Variant Call Format

The Variant Call Format (VCF) specifies the format of a text file used in bioinformatics for storing gene sequence variations. The format has been developed with the advent of large-scale genotyping and DNA sequencing projects, such as the 1000 Genomes Project. Existing formats for genetic data such as General feature format (GFF) stored all of the genetic data, much of which is redundant because it will be shared across the genomes. By using the variant call format only the variations need to be stored along with a reference genome.

The standard is currently in version 4.3,^[1][2] although the 1000 Genomes Project has developed their own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.^[3] A set of tools is also available for editing and manipulating the files.^[4]

Example

##fileformat=VCFv4.3
##fileDate=20090805
##source=myImputationProgramV3.1
##reference=file:///seq/references/1000GenomesPilot-NCBI36.fasta
##contig=<ID=20,length=62435964,assembly=B36,md5=f126cdf8a6e0c7f379d618ff66beb2da,species="Homo sapiens",taxonomy=x>
##phasing=partial
##INFO=<ID=NS,Number=1,Type=Integer,Description="Number of Samples With Data">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Total Depth">
##INFO=<ID=AF,Number=A,Type=Float,Description="Allele Frequency">
##INFO=<ID=AA,Number=1,Type=String,Description="Ancestral Allele">
##INFO=<ID=DB,Number=0,Type=Flag,Description="dbSNP membership, build 129">
##INFO=<ID=H2,Number=0,Type=Flag,Description="HapMap2 membership">
##FILTER=<ID=q10,Description="Quality below 10">
##FILTER=<ID=s50,Description="Less than 50% of samples have data">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=HQ,Number=2,Type=Integer,Description="Haplotype Quality">
#CHROM POS      ID         REF   ALT    QUAL  FILTER   INFO                             FORMAT       NA00001         NA00002          NA00003
20     14370    rs6054257  G     A      29    PASS    NS=3;DP=14;AF=0.5;DB;H2           GT:GQ:DP:HQ  0|0:48:1:51,51  1|0:48:8:51,51   1/1:43:5:.,.
20     17330    .          T     A      3     q10     NS=3;DP=11;AF=0.017               GT:GQ:DP:HQ  0|0:49:3:58,50  0|1:3:5:65,3     0/0:41:3
20     1110696  rs6040355  A     G,T    67    PASS    NS=2;DP=10;AF=0.333,0.667;AA=T;DB GT:GQ:DP:HQ  1|2:21:6:23,27  2|1:2:0:18,2     2/2:35:4
20     1230237  .          T     .      47    PASS    NS=3;DP=13;AA=T                   GT:GQ:DP:HQ  0|0:54:7:56,60  0|0:48:4:51,51   0/0:61:2
20     1234567  microsat1  GTC   G,GTCT 50    PASS    NS=3;DP=9;AA=G                    GT:GQ:DP     0/1:35:4        0/2:17:2         1/1:40:3

The VCF header

The header begins the file and provides metadata describing the body of the file. Header lines are denoted as starting with #. Special keywords in the header are denoted with ##. Recommended keywords include fileformat, fileDate and reference.

The header contains keywords that optionally semantically and syntactically describe the fields used in the body of the file, notably INFO, FILTER, and FORMAT (see below).

The columns of a VCF

The body of VCF follows the header, and is tab separated into 8 mandatory columns and an unlimited number of optional columns that may be used to record other information about the sample(s). When additional columns are used, the first optional column is used to describe the format of the data in the columns that follow.

Common INFO fields

Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional):

AA 

ancestral allele

AC 

allele count in genotypes, for each ALT allele, in the same order as listed

AF 

allele frequency for each ALT allele in the same order as listed: use this when estimated from primary data, not called genotypes

AN 

total number of alleles in called genotypes

BQ 

RMS base quality at this position

CIGAR 

cigar string describing how to align an alternate allele to the reference allele

DB 

dbSNP membership

DP 

combined depth across samples, e.g. DP=154

END 

end position of the variant described in this record (for use with symbolic alleles)

H2 

membership in hapmap2

H3 

membership in hapmap3

MQ 

RMS mapping quality, e.g. MQ=52

MQ0 

Number of MAPQ == 0 reads covering this record

NS 

Number of samples with data

SB 

strand bias at this position

SOMATIC 

indicates that the record is a somatic mutation, for cancer genomics

VALIDATED 

validated by follow-up experiment

1000G 

membership in 1000 Genomes

See also

• The Genome Variation Format (GVF), an extension based on the GFF3 format.

The VCF specification is no longer maintained by the 1000 Genomes Project. The group leading the management and expansion of the format is the Global Alliance for Genomics and Health Data Working group file format team, http://ga4gh.org/#/fileformats-team

External links

• An explanation of the format in picture form
• Free, graphical tool to inspect, search, split and merge VCF files on OS X
• Ossola, Alexandra (20 March 2015). "The Race to Build a Search Engine for Your DNA". IEEE Spectrum. Retrieved March 2015. Check date values in: |access-date= (help)

References