db nfsp information

gistfile1.txt

dbNSFP version 3.0b2a

Release:
	April 12, 2015
	
Major sources:
	Variant determination:
		Gencode release 22/Ensembl 79, released March, 2015 (hg38)
	Functional predictions:
		SIFT ensembl 66, released Jan, 2015 http://provean.jcvi.org/index.php
		PROVEAN 1.1 ensembl 66, released Jan, 2015 http://provean.jcvi.org/index.php
		Polyphen-2 v2.2.2, released Feb, 2012 http://genetics.bwh.harvard.edu/pph2/
		LRT, released November, 2009 http://www.genetics.wustl.edu/jflab/lrt_query.html
		MutationTaster 2, data retrieved in 2015 http://www.mutationtaster.org/
		MutationAssessor, release 2 http://mutationassessor.org/
		FATHMM, v2.3 http://fathmm.biocompute.org.uk
		CADD, v1.2 http://cadd.gs.washington.edu/
		VEST, v3.0 http://karchinlab.org/apps/appVest.html
	Conservation scores:
		phyloP7way_vertebrate (hg38) http://hgdownload.soe.ucsc.edu/goldenPath/hg38/phyloP7way/
		phastCons7way_vertebrate (hg38) http://hgdownload.soe.ucsc.edu/goldenPath/hg38/phastCons7way/
		GERP++ http://mendel.stanford.edu/SidowLab/downloads/gerp/
		SiPhy http://www.broadinstitute.org/mammals/2x/siphy_hg19/
	Other variant annotation sources:
		Interpro http://www.ebi.ac.uk/interpro/
		1000 Genomes project http://www.1000genomes.org/
		ESP http://evs.gs.washington.edu/EVS/
		dbSNP 142 (hg38) ftp://ftp.ncbi.nih.gov/snp/organisms/human_9606_b142_GRCh38/VCF/
		clinvar 20150305 (hg38) ftp://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/
		ExAC v0.3 http://exac.broadinstitute.org/
		UK10K COHORT http://www.uk10k.org/studies/cohorts.html
		Ancestral alleles ftp://ftp.ebi.ac.uk/pub/databases/ensembl/ancestral_alleles/
		RSRS http://dx.doi.org/10.1016/j.ajhg.2012.03.002
	Other gene annotation sources:
		HGNC, downloaded on March 27, 2015
		Uniprot, released March, 2015
		IntAct, downloaded on March 27, 2015
		GWAS catalog, downloaded on March 27, 2015
		egenetics and GNF/Atlas expression data, downloaded from BioMart on Oct. 1, 2013
		BioGRID, version 3.3.122
		Haploinsufficiency probability data, from doi:10.1371/journal.pgen.1001154
		Recessive probability data, from DOI:10.1126/science.1215040
		Residual Variation Intolerance Score (RVIS), from doi:10.1371/journal.pgen.1003709
		GO, downloaded on March 27, 2015
		ConsensusPathDB, Release 30
		Essential genes, based on doi:10.1371/journal.pgen.1003484
		Mouse genes, from ftp://ftp.informatics.jax.org/pub/reports/index.html on March 27, 2015
		Zebra fish genes, from http://zfin.org/downloads/pheno.txt on March 27, 2015
		KEGG pathway, from http://www.openbioinformatics.org/gengen/tutorial_calculate_gsea.html
		BioCarta pathway, from http://www.openbioinformatics.org/gengen/tutorial_calculate_gsea.html
		Ancestral allele: ftp://ftp.ebi.ac.uk/pub/databases/ensembl/ancestral_alleles/
		Altai Neanderthal genotypes: http://cdna.eva.mpg.de/neandertal/altai/AltaiNeandertal/VCF/
		Denisova genotypes: http://www.eva.mpg.de/denisova
		

Files:
	dbNSFP3.0b2a_variant.chr<#>     - dbNSFP variant database files by chromosomes
	dbNSFP3.0b2_gene                - dbNSFP gene database file
	dbNSFP3.0b2_gene.complete       - dbNSFP gene database file with complete interaction columns
	dbscSNV1.1.chr<#>               - scSNV database v1.1 files by chromosomes
	dbNSFP3.0b2a.readme.txt         - this file
	search_dbNSFP30b2a.class        - companion Java program for searching dbNSFP2.6
	search_dbNSFP30b2a.readme.pdf   - README file for search_dbNSFP26.class
	tryhg19.in                      - an example input file with hg19 genome positions
	tryhg18.in                      - an example input file with hg18 genome positions
	tryhg38.in                      - an example input file with hg38 genome positions
	try.vcf                         - an example of vcf input file


Description:
	The dbNSFP is an integrated database of functional annotations from multiple 
	sources for the comprehensive collection of human non-synonymous SNPs (nsSNVs). 
	Its current version includes a total of 82,832,027 nsSNVs and ssSNVs (splicing-site
	SNVs). It compiles prediction scores from 11 prediction algorithms (SIFT, Polyphen2, 
	LRT, MutationTaster2, MutationAssessor, FATHMM, MetaSVM, MetaLR, CADD, VEST, PROVEAN), 
	4 conservation scores (phyloP7way, phastCons7way, GERP++ and SiPhy) and other 
	function annotations. 
	Since version 2.0, dbNSFP is separated into two parts, dbNSFP_variant and 
	dbNSFP_gene. As their names indicate, the former focuses on variant annotations 
	(including prediction scores and conservation scores), and the latter focuses on 
	gene annotations.
	Since version 2.6, dbscSNV is added as an attached database, which includes all 
	potential human SNVs within splicing consensus regions (−3 to +8 at the 5’ splice site 
	and −12 to +2 at the 3’ splice site), i.e. scSNVs, and predictions for their potential 
	of altering splicing. 
	

Columns of dbNSFP_variant:
1	chr: chromosome number
2	pos(1-based): physical position on the chromosome as to hg38 (1-based coordinate).
		For mitochondrial SNV, this position refers to the rCRS (GenBank: NC_012920). 
3	ref: reference nucleotide allele (as on the + strand)
4	alt: alternative nucleotide allele (as on the + strand)
5	aaref: reference amino acid
		"." if the variant is a splicing site SNP (2bp on each end of an intron)
6	aaalt: alternative amino acid
		"." if the variant is a splicing site SNP (2bp on each end of an intron)
7	rs_dbSNP142: rs number from dbSNP 142
8	hg19_chr: chromosome as to hg19, "." means missing
9	hg19_pos(1-based): physical position on the chromosome as to hg19 (1-based coordinate).
		For mitochondrial SNV, this position refers to a YRI sequence (GenBank: AF347015)
10	hg18_chr: chromosome as to hg18, "." means missing
11	hg18_pos(1-based): physical position on the chromosome as to hg18 (1-based coordinate)
		For mitochondrial SNV, this position refers to a YRI sequence (GenBank: AF347015)
12	genename: gene name; if the nsSNV can be assigned to multiple genes, gene names are
		separated by ";"
13	cds_strand: coding sequence (CDS) strand (+ or -)
14	refcodon: reference codon
15	codonpos: position on the codon (1, 2 or 3)
16	codon_degeneracy: degenerate type (0, 2 or 3)
17	Ancestral_allele: the ancestral allele.
		Ancestral alleles of the mitochondrial genome are from RSRS. 
		Ancestral alleles of autosomes and X/Y chromosomes are provided by VEP based on 
		Ensembl 71. The following comes from its original README file:
		ACTG - high-confidence call, ancestral state supported by the other two sequences
		actg - low-confidence call, ancestral state supported by one sequence only
		N    - failure, the ancestral state is not supported by any other sequence
		-    - the extant species contains an insertion at this position
		.    - no coverage in the alignment
18	AltaiNeandertal: genotype of a deep sequenced Altai Neanderthal
19	Denisova: genotype of a deep sequenced Denisova
20	Ensembl_geneid: Ensembl gene id
21	Ensembl_transcriptid: Ensembl transcript ids (Multiple entries separated by ";")
22	Ensembl_proteinid: Ensembl protein ids
		Multiple entries separated by ";",  corresponding to Ensembl_transcriptids
23	aapos: amino acid position as to the protein.
		"-1" if the variant is a splicing site SNP (2bp on each end of an intron). 
		Multiple entries separated by ";", corresponding to Ensembl_proteinid
24	SIFT_score: SIFT score (SIFTori). Scores range from 0 to 1. The smaller the score the
		more likely the SNP has damaging effect. 
		Multiple scores separated by ";", corresponding to Ensembl_proteinid.
25	SIFT_converted_rankscore: SIFTori scores were first converted to SIFTnew=1-SIFTori,
		then ranked among all SIFTnew scores in dbNSFP. The rankscore is the ratio of 
		the rank the SIFTnew score over the total number of SIFTnew scores in dbNSFP. 
		If there are multiple scores, only the most damaging (largest) rankscore is presented.
		The rankscores range from 0.00963 to 0.91219.
26	SIFT_pred: If SIFTori is smaller than 0.05 (rankscore>0.395) the corresponding nsSNV is
		predicted as "D(amaging)"; otherwise it is predicted as "T(olerated)". 
		Multiple predictions separated by ";"
27	Uniprot_acc_Polyphen2: Uniprot accession number provided by Polyphen2.
		Multiple entries separated by ";".
28	Uniprot_id_Polyphen2: Uniprot ID numbers corresponding to Uniprot_acc_Polyphen2.
		Multiple entries separated by ";".
29	Uniprot_aapos_Polyphen2: amino acid position as to Uniprot_acc_Polyphen2.
		Multiple entries separated by ";".
30	Polyphen2_HDIV_score: Polyphen2 score based on HumDiv, i.e. hdiv_prob.
		The score ranges from 0 to 1. 
		Multiple entries separated by ";", corresponding to Uniprot_acc_Polyphen2.
31	Polyphen2_HDIV_rankscore: Polyphen2 HDIV scores were first ranked among all HDIV scores
		in dbNSFP. The rankscore is the ratio of the rank the score over the total number of 
		the scores in dbNSFP. If there are multiple scores, only the most damaging (largest) 
		rankscore is presented. The scores range from 0.02634 to 0.89865.
32	Polyphen2_HDIV_pred: Polyphen2 prediction based on HumDiv, "D" ("probably damaging",
		HDIV score in [0.957,1] or rankscore in [0.52844,0.89865]), "P" ("possibly damaging", 
		HDIV score in [0.453,0.956] or rankscore in [0.34282,0.52689]) and "B" ("benign", 
		HDIV score in [0,0.452] or rankscore in [0.02634,0.34268]). Score cutoff for binary 
		classification is 0.5 for HDIV score or 0.3528 for rankscore, i.e. the prediction is 
		"neutral" if the HDIV score is smaller than 0.5 (rankscore is smaller than 0.3528), 
		and "deleterious" if the HDIV score is larger than 0.5 (rankscore is larger than 
		0.3528). Multiple entries are separated by ";".
33	Polyphen2_HVAR_score: Polyphen2 score based on HumVar, i.e. hvar_prob.
		The score ranges from 0 to 1. 
		Multiple entries separated by ";", corresponding to Uniprot_acc_Polyphen2.
34	Polyphen2_HVAR_rankscore: Polyphen2 HVAR scores were first ranked among all HVAR scores
		in dbNSFP. The rankscore is the ratio of the rank the score over the total number of 
		the scores in dbNSFP. If there are multiple scores, only the most damaging (largest) 
		rankscore is presented. The scores range from 0.01257 to 0.97092.
35	Polyphen2_HVAR_pred: Polyphen2 prediction based on HumVar, "D" ("probably damaging",
		HVAR score in [0.909,1] or rankscore in [0.62797,0.97092]), "P" ("possibly damaging", 
		HVAR in [0.447,0.908] or rankscore in [0.44195,0.62727]) and "B" ("benign", HVAR 
		score in [0,0.446] or rankscore in [0.01257,0.44151]). Score cutoff for binary 
		classification is 0.5 for HVAR score or 0.45833 for rankscore, i.e. the prediction 
		is "neutral" if the HVAR score is smaller than 0.5 (rankscore is smaller than 
		0.45833), and "deleterious" if the HVAR score is larger than 0.5 (rankscore is larger 
		than 0.45833). Multiple entries are separated by ";".
36	LRT_score: The original LRT two-sided p-value (LRTori), ranges from 0 to 1.
37	LRT_converted_rankscore: LRTori scores were first converted as LRTnew=1-LRTori*0.5 if
		Omega<1, or LRTnew=LRTori*0.5 if Omega>=1. Then LRTnew scores were ranked among all 
		LRTnew scores in dbNSFP. The rankscore is the ratio of the rank over the total number 
		of the scores in dbNSFP. The scores range from 0.00162 to 0.84324.
38	LRT_pred: LRT prediction, D(eleterious), N(eutral) or U(nknown), which is not solely
		determined by the score. 
39	LRT_Omega: estimated nonsynonymous-to-synonymous-rate ratio (Omega, reported by LRT)
40	MutationTaster_score: MutationTaster p-value (MTori), ranges from 0 to 1. 
		Multiple scores are separated by ";". Information on corresponding transcript(s) can 
		be found by querying http://www.mutationtaster.org/ChrPos.html
41	MutationTaster_converted_rankscore: The MTori scores were first converted: if the prediction
		is "A" or "D" MTnew=MTori; if the prediction is "N" or "P", MTnew=1-MTori. Then MTnew 
		scores were ranked among all MTnew scores in dbNSFP. If there are multiple scores of a 
		SNV, only the largest MTnew was used in ranking. The rankscore is the ratio of the
		rank of the score over the total number of MTnew scores in dbNSFP. The scores range
		from 0.08977 to 0.81031.
42	MutationTaster_pred: MutationTaster prediction, "A" ("disease_causing_automatic"),
		"D" ("disease_causing"), "N" ("polymorphism") or "P" ("polymorphism_automatic"). The 
		score cutoff between "D" and "N" is 0.5 for MTnew and 0.31709 for the rankscore.
43	MutationTaster_model: MutationTaster prediction models.
44	MutationTaster_AAE: MutationTaster predicted amino acid change.
45	Uniprot_id_MutationAssessor: Uniprot ID number provided by MutationAssessor.
46	Uniprot_variant_MutationAssessor: AA variant as to Uniprot_id_MutationAssessor.
47	MutationAssessor_score: MutationAssessor functional impact combined score (MAori). The
		score ranges from -5.545 to 5.975 in dbNSFP. 
48	MutationAssessor_rankscore: MAori scores were ranked among all MAori scores in dbNSFP.
		The rankscore is the ratio of the rank of the score over the total number of MAori 
		scores in dbNSFP. The scores range from 0 to 1.
49	MutationAssessor_pred: MutationAssessor's functional impact of a variant :
		predicted functional, i.e. high ("H") or medium ("M"), or predicted non-functional,
		i.e. low ("L") or neutral ("N"). The MAori score cutoffs between "H" and "M", 
		"M" and "L", and "L" and "N", are 3.5, 1.9 and 0.8, respectively. The rankscore cutoffs 
		between "H" and "M", "M" and "L", and "L" and "N", are 0.941, 0.61456 and 0.26284, 
		respectively.
50	FATHMM_score: FATHMM default score (weighted for human inherited-disease mutations with
		Disease Ontology) (FATHMMori). Scores range from -16.13 to 10.64. The smaller the score 
		the more likely the SNP has damaging effect.
		Multiple scores separated by ";", corresponding to Ensembl_proteinid.
51	FATHMM_converted_rankscore: FATHMMori scores were first converted to
		FATHMMnew=1-(FATHMMori+16.13)/26.77, then ranked among all FATHMMnew scores in dbNSFP. 
		The rankscore is the ratio of the rank of the score over the total number of FATHMMnew 
		scores in dbNSFP. If there are multiple scores, only the most damaging (largest) 
		rankscore is presented. The scores range from 0 to 1.
52	FATHMM_pred: If a FATHMMori score is <=-1.5 (or rankscore >=0.81332) the corresponding nsSNV
		is predicted as "D(AMAGING)"; otherwise it is predicted as "T(OLERATED)".
		Multiple predictions separated by ";", corresponding to Ensembl_proteinid.
53	PROVEAN_score: PROVEAN score (PROVEANori). Scores range from -14 to 14. The smaller the score
		the more likely the SNP has damaging effect. 
		Multiple scores separated by ";", corresponding to Ensembl_proteinid.
54	PROVEAN_converted_rankscore: PROVEANori were first converted to PROVEANnew=1-(PROVEANori+14)/28,
		then ranked among all PROVEANnew scores in dbNSFP. The rankscore is the ratio of 
		the rank the PROVEANnew score over the total number of PROVEANnew scores in dbNSFP. 
		If there are multiple scores, only the most damaging (largest) rankscore is presented.
		The scores range from 0 to 1.
55	PROVEAN_pred: If PROVEANori <= -2.5 (rankscore>=0.543) the corresponding nsSNV is
		predicted as "D(amaging)"; otherwise it is predicted as "N(eutral)". 
		Multiple predictions separated by ";", corresponding to Ensembl_proteinid.
56	Transcript_id_VEST3: Transcript id provided by VEST3.
57	Transcript_var_VEST3: amino acid change as to Transcript_id_VEST3.
58	VEST3_score: VEST 3.0 score. Score ranges from 0 to 1. The larger the score the more likely
		the mutation may cause functional change. 
		Multiple scores separated by ";", corresponding to Transcript_id_VEST3.
		Please note this score is free for non-commercial use. For more details please refer to 
		http://wiki.chasmsoftware.org/index.php/SoftwareLicense. Commercial users should contact 
		the Johns Hopkins Technology Transfer office.
59	VEST3_rankscore: VEST3 scores were ranked among all VEST3 scores in dbNSFP.
		The rankscore is the ratio of the rank of the score over the total number of VEST3 
		scores in dbNSFP. In case there are multiple scores for the same variant, the largest 
		score (most damaging) is presented. The scores range from 0 to 1. 
		Please note VEST score is free for non-commercial use. For more details please refer to 
		http://wiki.chasmsoftware.org/index.php/SoftwareLicense. Commercial users should contact 
		the Johns Hopkins Technology Transfer office.
60	CADD_raw: CADD raw score for functional prediction of a SNP. Please refer to Kircher et al.
		(2014) Nature Genetics 46(3):310-5 for details. The larger the score the more likely
		the SNP has damaging effect. Please note the following copyright statement for CADD: 
		"CADD scores (http://cadd.gs.washington.edu/) are Copyright 2013 University of 
		Washington and Hudson-Alpha Institute for Biotechnology (all rights reserved) but are 
		freely available for all academic, non-commercial applications. For commercial 
		licensing information contact Jennifer McCullar (mccullaj@uw.edu)."
61	CADD_raw_rankscore: CADD raw scores were ranked among all CADD raw scores in dbNSFP. The
		rankscore is the ratio of the rank of the score over the total number of CADD 
		raw scores in dbNSFP. Please note the following copyright statement for CADD: "CADD 
		scores (http://cadd.gs.washington.edu/) are Copyright 2013 University of Washington 
		and Hudson-Alpha Institute for Biotechnology (all rights reserved) but are freely 
		available for all academic, non-commercial applications. For commercial licensing 
		information contact Jennifer McCullar (mccullaj@uw.edu)."
62	CADD_phred: CADD phred-like score. This is phred-like rank score based on whole genome
		CADD raw scores. Please refer to Kircher et al. (2014) Nature Genetics 46(3):310-5 
		for details. The larger the score the more likely the SNP has damaging effect. 
		Please note the following copyright statement for CADD: "CADD scores 
		(http://cadd.gs.washington.edu/) are Copyright 2013 University of Washington and 
		Hudson-Alpha Institute for Biotechnology (all rights reserved) but are freely 
		available for all academic, non-commercial applications. For commercial licensing 
		information contact Jennifer McCullar (mccullaj@uw.edu)."
63	MetaSVM_score: Our support vector machine (SVM) based ensemble prediction score, which
		incorporated 10 scores (SIFT, PolyPhen-2 HDIV, PolyPhen-2 HVAR, GERP++, MutationTaster, 
		Mutation Assessor, FATHMM, LRT, SiPhy, PhyloP) and the maximum frequency observed in 
		the 1000 genomes populations. Larger value means the SNV is more likely to be damaging. 
		Scores range from -2 to 3 in dbNSFP.
64	MetaSVM_rankscore: MetaSVM scores were ranked among all MetaSVM scores in dbNSFP.
		The rankscore is the ratio of the rank of the score over the total number of MetaSVM 
		scores in dbNSFP. The scores range from 0 to 1.
65	MetaSVM_pred: Prediction of our SVM based ensemble prediction score,"T(olerated)" or
		"D(amaging)". The score cutoff between "D" and "T" is 0. The rankscore cutoff between
		"D" and "T" is 0.82268.
66	MetaLR_score: Our logistic regression (LR) based ensemble prediction score, which
		incorporated 10 scores (SIFT, PolyPhen-2 HDIV, PolyPhen-2 HVAR, GERP++, MutationTaster, 
		Mutation Assessor, FATHMM, LRT, SiPhy, PhyloP) and the maximum frequency observed in 
		the 1000 genomes populations. Larger value means the SNV is more likely to be damaging. 
		Scores range from 0 to 1.
67	MetaLR_rankscore: MetaLR scores were ranked among all MetaLR scores in dbNSFP. The rankscore
		is the ratio of the rank of the score over the total number of MetaLR scores in dbNSFP. 
		The scores range from 0 to 1.
68	MetaLR_pred: Prediction of our MetaLR based ensemble prediction score,"T(olerated)" or
		"D(amaging)". The score cutoff between "D" and "T" is 0.5. The rankscore cutoff between 
		"D" and "T" is 0.81113.
69	Reliability_index: Number of observed component scores (except the maximum frequency in
		the 1000 genomes populations) for MetaSVM and MetaLR. Ranges from 1 to 10. As MetaSVM 
		and MetaLR scores are calculated based on imputed data, the less missing component 
		scores, the higher the reliability of the scores and predictions. 
70	GERP++_NR: GERP++ neutral rate
71	GERP++_RS: GERP++ RS score, the larger the score, the more conserved the site.
72	GERP++_RS_rankscore: GERP++ RS scores were ranked among all GERP++ RS scores in dbNSFP.
		The rankscore is the ratio of the rank of the score over the total number of GERP++ RS 
		scores in dbNSFP.
73	phyloP7way_vertebrate: phyloP (phylogenetic p-values) conservation score based on the
		multiple alignments of 7 vertebrate genomes (including human). The larger the score, 
		the more conserved the site.
74	phyloP7way_vertebrate_rankscore: phyloP7way_vertebrate scores were ranked among all
		phyloP7way_vertebrate scores in dbNSFP. The rankscore is the ratio of the rank of the 
		score over the total number of phyloP7way_vertebrate scores in dbNSFP.
75	phastCons7way_vertebrate: phastCons conservation score based on the multiple alignments
		of 7 vertebrate genomes (including human). The larger the score, the more conserved 
		the site.
76	phastCons7way_vertebrate_rankscore: phastCons7way_vertebrate scores were ranked among
		all phastCons7way_vertebrate scores in dbNSFP. The rankscore is the ratio of the rank 
		of the score over the total number of phastCons7way_vertebrate scores in dbNSFP.
77	SiPhy_29way_pi: The estimated stationary distribution of A, C, G and T at the site,
		using SiPhy algorithm based on 29 mammals genomes. 
78	SiPhy_29way_logOdds: SiPhy score based on 29 mammals genomes. The larger the score,
		the more conserved the site.
79	SiPhy_29way_logOdds_rankscore: SiPhy_29way_logOdds scores were ranked among all
		SiPhy_29way_logOdds scores in dbNSFP. The rankscore is the ratio of the rank 
		of the score over the total number of SiPhy_29way_logOdds scores in dbNSFP.
80	1000Gp3_AC: Alternative allele counts in the whole 1000 genomes phase 3 (1000Gp3) data.
81	1000Gp3_AF: Alternative allele frequency in the whole 1000Gp3 data.
82	1000Gp3_AFR_AC: Alternative allele counts in the 1000Gp3 African descendent samples.
83	1000Gp3_AFR_AF: Alternative allele frequency in the 1000Gp3 African descendent samples.
84	1000Gp3_EUR_AC: Alternative allele counts in the 1000Gp3 European descendent samples.
85	1000Gp3_EUR_AF: Alternative allele frequency in the 1000Gp3 European descendent samples.
86	1000Gp3_AMR_AC: Alternative allele counts in the 1000Gp3 American descendent samples.
87	1000Gp3_AMR_AF: Alternative allele frequency in the 1000Gp3 American descendent samples.
88	1000Gp3_EAS_AC: Alternative allele counts in the 1000Gp3 East Asian descendent samples.
89	1000Gp3_EAS_AF: Alternative allele frequency in the 1000Gp3 East Asian descendent samples.
90	1000Gp3_SAS_AC: Alternative allele counts in the 1000Gp3 South Asian descendent samples.
91	1000Gp3_SAS_AF: Alternative allele frequency in the 1000Gp3 South Asian descendent samples.
92	TWINSUK_AC: Alternative allele count in called genotypes in UK10K TWINSUK cohort.
93	TWINSUK_AF: Alternative allele frequency in called genotypes in UK10K TWINSUK cohort.
94	ALSPAC_AC: Alternative allele count in called genotypes in UK10K TWINSUK cohort.
95	ALSPAC_AF: Alternative allele frequency in called genotypes in UK10K TWINSUK cohort.
96	ESP6500_AA_AC: Alternative allele count in the African American samples of the
		NHLBI GO Exome Sequencing Project (ESP6500 data set).
97	ESP6500_AA_AF: Alternative allele frequency in the African American samples of the
		NHLBI GO Exome Sequencing Project (ESP6500 data set).
98	ESP6500_EA_AC: Alternative allele count in the European American samples of the
		NHLBI GO Exome Sequencing Project (ESP6500 data set).
99	ESP6500_EA_AF: Alternative allele frequency in the European American samples of the
		NHLBI GO Exome Sequencing Project (ESP6500 data set).
100	ExAC_AC: Allele count in total ExAC samples (~60,706 unrelated individuals)
101	ExAC_AF: Allele frequency in total ExAC samples
102	ExAC_Adj_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in total ExAC samples
103	ExAC_Adj_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in total ExAC samples
104	ExAC_AFR_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in African & African American
		ExAC samples
105	ExAC_AFR_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in African & African American
		ExAC samples
106	ExAC_AMR_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in American ExAC samples
107	ExAC_AMR_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in American ExAC samples
108	ExAC_EAS_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in East Asian ExAC samples
109	ExAC_EAS_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in East Asian ExAC samples
110	ExAC_FIN_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in Finnish ExAC samples
111	ExAC_FIN_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in Finnish ExAC samples
112	ExAC_NFE_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in Non-Finnish European ExAC
		samples
113	ExAC_NFE_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in Non-Finnish European ExAC
		samples
114	ExAC_SAS_AC: Adjusted Alt allele counts (DP >= 10 & GQ >= 20) in South Asian ExAC samples
115	ExAC_SAS_AF: Adjusted Alt allele frequency (DP >= 10 & GQ >= 20) in South Asian ExAC samples
116	clinvar_rs: rs number from the clinvar data set
117	clinvar_clnsig: clinical significance as to the clinvar data set
		2 - Benign, 3 - Likely benign, 4 - Likely pathogenic, 5 - Pathogenic, 6 - drug response, 
		7 - histocompatibility. A negative score means the the score is for the ref allele
118	clinvar_trait: the trait/disease the clinvar_clnsig referring to
119	Interpro_domain: domain or conserved site on which the variant locates. Domain
		annotations come from Interpro database. The number in the brackets following
		a specific domain is the count of times Interpro assigns the variant position to  
		that domain, typically coming from different predicting databases. Multiple entries 
		separated by ";".

	
	Note 1: Missing data is designated as '.'. 

Columns of dbNSFP_gene:
	Gene_name: Gene symbol from HGNC
	Ensembl_gene: Ensembl gene id (from HGNC)
	chr: Chromosome number (from HGNC)
120	Gene_old_names: Old gene symbol (from HGNC)
121	Gene_other_names: Other gene names (from HGNC)
122	Uniprot_acc(HGNC/Uniprot): Uniprot acc number (from HGNC and Uniprot)
123	Uniprot_id(HGNC/Uniprot): Uniprot id (from HGNC and Uniprot)
124	Entrez_gene_id: Entrez gene id (from HGNC)
125	CCDS_id: CCDS id (from HGNC)
126	Refseq_id: Refseq gene id (from HGNC)
127	ucsc_id: UCSC gene id (from HGNC)
128	MIM_id: MIM gene id (from HGNC)
129	Gene_full_name: Gene full name (from HGNC)
130	Pathway(Uniprot): Pathway description from Uniprot
131	Pathway(BioCarta)_short: Short name of the Pathway(s) the gene belongs to (from BioCarta)
132	Pathway(BioCarta)_full: Full name(s) of the Pathway(s) the gene belongs to (from BioCarta)
133	Pathway(ConsensusPathDB): Pathway(s) the gene belongs to (from ConsensusPathDB)
134	Pathway(KEGG)_id: ID(s) of the Pathway(s) the gene belongs to (from KEGG)
135	Pathway(KEGG)_full: Full name(s) of the Pathway(s) the gene belongs to (from KEGG)
136	Function_description: Function description of the gene (from Uniprot)
137	Disease_description: Disease(s) the gene caused or associated with (from Uniprot)
138	MIM_phenotype_id: MIM id(s) of the phenotype the gene caused or associated with (from Uniprot)
139	MIM_disease: MIM disease name(s) with MIM id(s) in "[]" (from Uniprot)
140	Trait_association(GWAS): Trait(s) the gene associated with (from GWAS catalog)
141	GO_biological_process: GO terms for biological process
142	GO_cellular_component: GO terms for cellular component
143	GO_molecular_function: GO terms for molecular function
144	Tissue_specificity(Uniprot): Tissue specificity description from Uniprot
145	Expression(egenetics): Tissues/organs the gene expressed in (egenetics data from BioMart)
146	Expression(GNF/Atlas): Tissues/organs the gene expressed in (GNF/Atlas data from BioMart)
147	Interactions(IntAct): The number of other genes this gene interacting with (from IntAct).
		Full information (gene name followed by Pubmed id in "[]") can be found in the ".complete"
		table
148	Interactions(BioGRID): The number of other genes this gene interacting with (from BioGRID)
		Full information (gene name followed by Pubmed id in "[]") can be found in the ".complete"
		table
149	Interactions(ConsensusPathDB): The number of other genes this gene interacting with
		(from ConsensusPathDB). Full information (gene name followed by Pubmed id in "[]") can be 
		found in the ".complete" table
150	P(HI): Estimated probability of haploinsufficiency of the gene
		(from doi:10.1371/journal.pgen.1001154)
151	P(rec): Estimated probability that gene is a recessive disease gene
		(from DOI:10.1126/science.1215040)
152	Known_rec_info: Known recessive status of the gene (from DOI:10.1126/science.1215040)
		"lof-tolerant = seen in homozygous state in at least one 1000G individual"
		"recessive = known OMIM recessive disease" 
		(original annotations from DOI:10.1126/science.1215040)
153	RVIS: Residual Variation Intolerance Score, a measure of intolerance of mutational burden,
		the higher the score the more tolerant to mutational burden the gene is. 
		from doi:10.1371/journal.pgen.1003709
154	RVIS_percentile: The percentile rank of the gene based on RVIS, the higher the percentile
		the more tolerant to mutational burden the gene is. 
155	Essential_gene: Essential ("E") or Non-essential phenotype-changing ("N") based on
		Mouse Genome Informatics database. from doi:10.1371/journal.pgen.1003484
156	MGI_mouse_gene: Homolog mouse gene name from MGI
157	MGI_mouse_phenotype: Phenotype description for the homolog mouse gene from MGI
158	ZFIN_zebrafish_gene: Homolog zebrafish gene name from ZFIN
159	ZFIN_zebrafish_structure: Affected structure of the homolog zebrafish gene from ZFIN
160	ZFIN_zebrafish_phenotype_quality: Phenotype description for the homolog zebrafish gene
		from ZFIN
161	ZFIN_zebrafish_phenotype_tag: Phenotype tag for the homolog zebrafish gene from ZFIN

Columns of dbscSNV1.1:
	chr: chromosome number
	pos: physical position on the chromosome as to hg19 (1-based coordinate)
	ref: reference nucleotide allele (as on the + strand)
	alt: alternative nucleotide allele (as on the + strand)
	hg38_chr: chromosome number as to hg38
	hg38_pos: physical position on the chromosome as to hg38 (1-based coordinate)
	RefSeq?: whether the SNV is a scSNV according to RefSeq
	Ensembl?: whether the SNV is a scSNV according to Ensembl
	RefSeq_region: functional region the SNV located according to RefSeq
	RefSeq_gene: gene name according to RefSeq
	RefSeq_functional_consequence: functional consequence of the SNV according to RefSeq
	RefSeq_id_c.change_p.change: SNV in format of c.change and p.change according to RefSeq
	Ensembl_region: functional region the SNV located according to Ensembl
	Ensembl_gene: gene id according to Ensembl
	Ensembl_functional_consequence: functional consequence of the SNV according to Ensembl
	Ensembl_id_c.change_p.change: SNV in format of c.change and p.change according to Ensembl
	ada_score: ensemble prediction score based on ada-boost. Ranges 0 to 1. The larger the 
		score the higher probability the scSNV will affect splicing. The suggested cutoff for
		a binary prediction (affecting splicing vs. not affecting splicing) is 0.6.
	rf_score: ensemble prediction score based on random forests. Ranges 0 to 1. The larger the 
		score the higher probability the scSNV will affect splicing. The suggested cutoff for
		a binary prediction (affecting splicing vs. not affecting splicing) is 0.6.
	
	Note 1: Missing data is designated as '.'. 
	Note 2: Multiple annotations are separated by ';'

Please cite:
	Liu X, Jian X, and Boerwinkle E. 2011. dbNSFP: a lightweight database of human 
		non-synonymous SNPs and their functional predictions. Human Mutation. 32:894-899.
	Liu X, Jian X, and Boerwinkle E. 2013. dbNSFP v2.0: A Database of Human Nonsynonymous 
		SNVs and Their Functional Predictions and Annotations. Human Mutation. 34:E2393-E2402. 

Contact:
	Xiaoming Liu, Ph.D.
	Assistant Professor,
	Human Genetics Center,
	School of Public Health,
	The University of Texas Health Science Center at Houston.
	Email: xmliu.uth{at}gmail.com 
	
Changelog:
	February 23, 2011: dbNSFP and search_dbNSFP v0.9 released.

	April 4, 2011: A bug related to the prediction scores of MutationTaster is fixed. dbNSFP v1.0 
	released. A change to the chromosome search order of the search_dbNSFP. A readme file added. 
	search_dbNSFP v1.0 released.

	May 30, 2011: dbNSFP and search_dbNSFP v1.1 released. Version 1.1 added the following entries: 
	rs numbers from UniSNP (a cleaned version of dbSNP build 129), allele frequency recorded in dbSNP, 
	allele frequency reported by 1000 Genomes Project, alternative gene names, descriptive gene name, 
	database cross references (gene IDs of HGNC, MIM, Ensembl and HPRD). The unziped database is 18Gb.

	May 31, 2011: dbNSFP_light and search_dbNSFP_light v1.0 released. dbNSFP_light v1.0 is a light 
	version of dbNSFP, which contains less annotation entries but some additional 9,285,316 NSs that 
	are not in CCDS version 20090327. Scores of PhyloP, SIFT, Polyphen2, LRT and MutationTaster are 
	included but missing data are not  imputed. Prediction of LRT and MutationTaster are also included, 
	as well as the omega estimated by LRT. The unziped database is 6Gb.
 
	October 24, 2011: dbNSFP_light v1.1 and search_dbNSFP_light v1.1 released. dbNSFP v1.2 and 
	search_dbNSFP v1.2 released. The new versions added GERP++ neutral rates and RS scores.

	October 25, 2011: dbNSFP v1.3 released. It added Uniprot ID, accession number and amino acid 
	position based on Polyphen-2 annotation. Users now can search amino acid change directly referring 
	to a Uniprot ID or accession number. 
 
	November 3, 2011: dbNSFP_light v1.2 released. It added Uniprot ID, accession number and amino acid 
	position based on Polyphen-2 annotation. Users now can search amino acid change directly referring 
	to a Uniprot ID or accession number.
 
	November 10, 2011:  A bug fixed in the companion search program for dbNSFP v1.3, which causes invalid 
	search using AA mutations with Uniprot ID or accession number.
 
	December 16, 2011: dbNSFP_light v1.3 released. It updated SIFT scores (August, 2011 version) and 
	Polyphen-2 scores (May, 2011 version). Uniprot ID, accession number and amino acid position based 
	on the Polyphen-2 annotations have been updated too.

	April 11, 2012: dbNSFP2.0b1_variant released. This is beta test version of the variant sub-database 
	of dbNSFP v2.0, which is rebuilt based on Gencode release 9 / Ensembl version 64.

	June 2, 2012: dbNSFP v2.0b2 released. It includes both the dbNSFP_variant and dbNSFP_gene sub-databases. 
	Slight changes have been made to the Ensembl gene and transcript ids of dbNSFP_variant in order to be 
	compatible to other database sources.

	July 2, 2012: dbNSFP v2.0b3 released. An additional 2.2 million splicing site SNPs have been added to 
	dbNSFP_variant. In the table those SNPs have missing (".") in aaref, aaalt and "-1" in aapos. There's 
	no change to the format of search input file.

	August 28, 2012: The companion java search program search_dbNSFP20b3 is updated. Added features include 
	supporting vcf file as input file and options for output contents (columns).

	October 27, 2012: dbNSFP v2.0b4 is released. A new functional prediction score MutationAssessor is added 
	(I thank Mr. Yevgeniy Antipin for his recommendation). Allele frequencies from ESP 5400 data set are 
	replaced by ESP 6500 data set.

	February 25, 2013: dbNSFP v2.0 is released. A new functional prediction score FATHMM is added.

	March 22, 2013: A bug which caused a lot of missing FATHMM scores has been fixed.  

	May 31, 2013: The source code of the companion Java search program is now available under the RECEX SHARED 
	SOURCE LICENSE.

	October 3, 2013: dbNSFP v2.1 is released. MutationTaster and FATHMM scores have been updated. Converted 
	scores of SIFT, LRT, MutationTaster, MutationAssessor and FATHMM have been added. Columns of SIFT and FATHMM 
	predictions have been added. The gene database has also been updated. Database IDs are updated. GO Slim terms, 
	pathway and protein interaction information from the ConsensusPathDB, and list of essential and non-essential 
	genes (based on phenotypes of mouse homologs) have been added.

	January 23, 2014: dbNSFP v2.2 is released. SIFT and FATHMM now have multiple scores corresponding to different 
	Ensembl ENSP ids and amino acid positions (aapos_SIFT and aapos_FATHMM). Accordingly, our companion search 
	program now supports SNP searches based on Ensembl ENSP ids and amino acid positions. A bug is fixed for a 
	small proportion of MutationTaster scores.

	January 26, 2014: dbNSFP v2.3 is released.  Two ensemble scores (RadialSVM and LR) and their predictions have 
	been added.

	February 12, 2014: A bug was fixed in dbNSFP v2.2 and v2.3, which caused missing delimiters in columns 
	aapos_SIFT, SIFT_score_converted and SIFT_pred. (I thank Mr. Yevgeniy Antipin for his reminder). 

	March 5, 2014: dbNSFP v2.4 is released. A whole genome functional prediction score called CADD was added, 
	along with five more conservation scores (phyloP46way_primate, phyloP100way_vertebrate, phastCons46way_primate, 
	phastCons46way_placental, phastCons100way_vertebarate). To facilitate comparison between scores, we added rank 
	scores for most functional prediction scores and conservation scores, and replacing the  "converted" scores in 
	the previous versions.

	June 1, 2014: dbNSFP v2.5 is released. A new functional score VEST 3.0 has been added. We thank Dr. Karchin for 
	kindly providing the score. A bug that causes the MutationTaster score error since v2.1 for variants with a 
	prediction of  "Polymorphism_automatic" has been fixed. We thank John McGuigan and James Ireland for reporting 
	this bug. As MutationTaster can also predict splicing change and other functional effects, in case a variant has 
	multiple predictions based on their different model, we took the most damaging score and prediction for dbNSFP. 
	
	July 26, 2014: dbNSFP v2.6 is released. rs numbers from dbSNP 141 have been added to the variant database files. 
	Mouse and zebra fish homolog genes and phenotypes have been added to the gene database file (I thank Alex Li for
	his suggestion and helps). Trait_association(GWAS) was also updated. An attached database called dbscSNV is 
	available for download. It includes all potential human SNVs within splicing consensus regions (−3 to +8 at the 
	5’ splice site and −12 to +2 at the 3’ splice site), i.e. scSNVs, related functional annotations and two ensemble 
	prediction scores for predicting their potential of altering splicing. A manuscript describing those scores have 
	been submitted. search_dbNSFP26 now supports searching dbNSFP along with dbscSNV using option "-s". 
	
	September 12, 2014: dbNSFP v2.7 is released. Chromosomes and positions of human reference hg38 have been added. 
	search_ dbNSFP27.class now supports query dbNSFP using the positions based on hg38 with the "-v hg38" option. 
	clinvar (freeze 20140902) annotations have been added. Allele frequencies from 2303 exomes of African Americans 
	and 3203 exomes of European Americans from the Atherosclerosis Risk in Communities Study (ARIC) cohort study 
	have been added. As the columns for gene interactions in dbNSFP_gene table contain very long strings, especially 
	for gene UBC, which may cause problems when viewing the results in Excel, now we only report the number of 
	interacting genes in those columns. Full information is retained in the dbNSFP_gene.complete table.
	
	November 21, 2014:  dbNSFP v2.8 is released. COSMIC (Catalogue Of Somatic Mutations In Cancer) annotation have 
	been added. Pathway information from BioCarta and KEGG (old version) has been added to the dbNSFP2.8_gene. A bug 
	causing inconsistency between MutationTaster scores and MutationTaster_pred, which affects v2.5 to v2.7, has 
	been fixed. I thank Adam Novak for reporting this bug.
	
	February 3, 2015: dbNSFP v2.9 is released. SIFT score has been updated to ensembl66 version. PROVEAN score 
	(Protein Variation Effect Analyzer) v1.1 has been added. I thank Yongwook Choi from jcvi for providing the SIFT 
	and PROVEAN scores. CADD score has been updated to 1.3 version. Please note the following copyright statement 
	for CADD: "CADD scores (http://cadd.gs.washington.edu/) are Copyright 2013 University of Washington and 
	Hudson-Alpha Institute for Biotechnology (all rights reserved) but are freely available for all academic, 
	non-commercial applications. For commercial licensing information contact Jennifer McCullar (mccullaj@uw.edu)."
	Allele frequency v0.3 of ~60,706 unrelated individuals from The Exome Aggregation Consortium (ExAC) has been added. 
	ExAC data are released under a Fort Lauderdale Agreement. Please refer to http://exac.broadinstitute.org/terms 
	for terms of use. I also want to thank Dr. CS (Jonathan) Liu from Softgenetics for providing hosting space.
	
	April 6, 2015: dbNSFP v3.0b1 is released. The core set of nsSNVs and ssSNVs has been rebuilt based on Gencode 22/
	Ensembl 79 with human reference sequence hg38. Putative genes have been included. Genes with incomplete 5' have
	been excluded (I thank Chris Gillies for reporting the issues for genes with incomplete 5' end.) Genes on 
	mitochondrial DNA have been included. Allele frequencies from the UK10K cohorts and genotypes of two Neanderthals 
	have been added. Some resources have been updated, including the MutationTaster (I thank Dr. Dominik Seelow 
	for kindly providing the scores), allele frequencies from the 1000 Genomes Project populations, ancestral alleles, 
	dbSNP, ClinVar and InterPro. The presentation of the prediction scores has been improved by adding columns for 
	the corresponding transcript/protein ids. PhyloP and PhastCons conservation scores based on hg19 have been 
	replaced by the scores based on hg38. Some resources have been dropped due to various reasons, including SLR 
	test statistic, UniSNP ids, allele frequencies from the ARIC cohorts and allele counts in COSMIC. dbNSFP_gene 
	has also been completely rebuilt using the up-to-date resources. Residual Variation Intolerance Scores (RVIS) 
	have been added. GO Slim terms have been replaced by full GO terms. Two branches of dbNSFP are now provided:
	dbNSFP3.0b1a suitable for academic use, which includes all the resources, and dbNSFP3.0b1c suitable for commercial 
	use, which does not include VEST3 and CADD. 
	
	April 12, 2015: dbNSFP v3.0b2 is released. This update fixed the issues due to inconsistent mitochondrial reference
	sequences used by different resources. I thank Dr. Lishuang Shen at MEEI for helping solving the issues. For 
	mitochondrial SNV, the pos (i.e. hg38) refers to the rCRS (GenBank: NC_012920) and hg19_pos refers to a YRI 
	sequence (GenBank: AF347015). The ancestral allele of mitochondrial SNV now comes from the Reconstructed Sapiens 
	Reference Sequence (RSRS, doi:10.1016/j.ajhg.2012.03.002). The affected content include ancestral alleles, 
	Neanderthal/Denisova genotypes and MutationTaster columns of the chrM file. The rankscores of MutationTaster has
	also been updated to reflect the update of its chrM scores. dbscSNV has been updated to v1.1 and added hg38 
	positions liftovered from its hg19 positions. Using search_dbNSFP30b2a or search_dbNSFP30b2c you can search 
	dbscSNV1.1 along with dbNSFP v3.0b2 with either hg19 coordinates or hg38 coordinates.