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, 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. A set of tools is also available for editing and manipulating the files.
##fileformat=VCFv4.0 ##fileDate=20110705 ##reference=1000GenomesPilot-NCBI37 ##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=.,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=GQ,Number=1,Type=Integer,Description="Genotype Quality"> ##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype"> ##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 Sample1 Sample2 Sample3 2 4370 rs6057 G A 29 . NS=2;DP=13;AF=0.5;DB;H2 GT:GQ:DP:HQ 0|0:48:1:52,51 1|0:48:8:51,51 1/1:43:5:.,. 2 7330 . T A 3 q10 NS=5;DP=12;AF=0.017 GT:GQ:DP:HQ 0|0:46:3:58,50 0|1:3:5:65,3 0/0:41:3 2 110696 rs6055 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 2 130237 . T . 47 . NS=2;DP=16;AA=T GT:GQ:DP:HQ 0|0:54:7:56,60 0|0:48:4:56,51 0/0:61:2 2 134567 microsat1 GTCT G,GTACT 50 PASS NS=2;DP=9;AA=G GT:GQ:DP 0/1:35:4 0/2:17:2 1/1:40:3 chr1 45796269 . G C chr1 45797505 . C G chr1 45798555 . T C chr1 45798901 . C T chr1 45805566 . G C chr2 47703379 . C T chr2 48010488 . G A chr2 48030838 . A T chr2 48032875 . CTAT - chr2 48032937 . T C chr2 48033273 . TTTTTGTTTTAATTCCT - chr2 48033551 . C G chr2 48033910 . A T chr2 215632048 . G T chr2 215632125 . TT - chr2 215632155 . T C chr2 215632192 . G A chr2 215632255 . CA TG chr2 215634055 . C T
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 nine columns of VCF
The body of VCF follows the header, and is tab separated into eight columns. An unlimited number of further columns give optional information about samples.
|Name||Brief description (see the specification for details).|
|1||CHROM||The name of the sequence (typically a chromosome) on which the variation is being called. This sequence is usually known as 'the reference sequence', i.e. the sequence against which the given sample varies.|
|2||POS||The 1-based position of the variation on the given sequence.|
|3||ID||The identifier of the variation, e.g. a dbSNP rs identifier or just . if unknown. Multiple identifiers should be separated by semi-colons without white-space.|
|4||REF||The reference base (or bases in the case of an indel) at the given position on the given reference sequence.|
|5||ALT||The list of alternative alleles at this position.|
|6||QUAL||A quality score associated with the inference of the given alleles.|
|7||FILTER||A flag indicating which of a given set of filters the variation has passed.|
|8||INFO||An extensible list of key-value pairs (fields) describing the variation. See below for some common fields. Multiple fields are separated by semicolons with optional values in the format: "<key>=[,data]".|
|9||FORMAT||An (optional) extensible list of fields for describing the samples. See below for some common fields.|
|+||SAMPLEs||For each (optional) sample described in the file, values are given for the fields listed in FORMAT|
Common INFO fields
Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional):
- ancestral allele
- allele count in genotypes, for each ALT allele, in the same order as listed
- allele frequency for each ALT allele in the same order as listed: use this when estimated from primary data, not called genotypes
- total number of alleles in called genotypes
- RMS base quality at this position
- cigar string describing how to align an alternate allele to the reference allele
- dbSNP membership
- combined depth across samples, e.g. DP=154
- end position of the variant described in this record (for use with symbolic alleles)
- membership in hapmap2
- membership in hapmap3
- RMS mapping quality, e.g. MQ=52
- Number of MAPQ == 0 reads covering this record
- Number of samples with data
- strand bias at this position
- indicates that the record is a somatic mutation, for cancer genomics
- validated by follow-up experiment
- membership in 1000 Genomes
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
- 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:
- "VCF Specification" (PDF). Retrieved 20 Oct 2016.
- "Specifications of SAM/BAM and related high-throughput sequencing file formats". Retrieved 24 June 2014.
- "Encoding Structural Variants in VCF (Variant Call Format) version 4.0 | 1000 Genomes". Retrieved 20 October 2016.
- "VCFtools from Github.io". Retrieved 20 October 2016.