View source for Variant Call Format

{{Infobox file format
| name = Variant Call Format
| type_code =
| uniform_type =
| conforms_to =
| magic =
| developer = VCFtools
| extended_from = Tab-separated values
| genre = [[Biology:Bioinformatics|Bioinformatics]]
| free = yes
| url = {{URL|https://github.com/samtools/hts-specs}}
}}

The '''Variant Call Format''' ('''VCF''') specifies the format of a text file used in [[Biology:Bioinformatics|bioinformatics]] for storing gene sequence variations. The format has been developed with the advent of large-scale [[Biology:Genotyping|genotyping]] and [[Biology:DNA sequencing|DNA sequencing]] projects, such as the [[Biology:1000 Genomes Project|1000 Genomes Project]]. Existing formats for genetic data such as [[General feature format|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,<ref name="vcf-spec">{{cite web|url=https://samtools.github.io/hts-specs/VCFv4.3.pdf|title=VCF Specification|accessdate=20 Oct 2016}}</ref><ref>{{cite web|url=https://github.com/samtools/hts-specs|title=Specifications of SAM/BAM and related high-throughput sequencing file formats|accessdate=24 June 2014}}</ref> although the [[Biology:1000 Genomes Project|1000 Genomes Project]] has developed its own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.<ref>{{cite web|url=http://www.internationalgenome.org/wiki/Analysis/Variant%20Call%20Format/VCF%20(Variant%20Call%20Format)%20version%204.0/encoding-structural-variants|title=Encoding Structural Variants in VCF (Variant Call Format) version 4.0 &#124; 1000 Genomes|accessdate=20 October 2016}}</ref>  There is also a '''Genomic VCF''' ('''gVCF''') extended format, which includes additional information about "blocks" that match the reference and their qualities.<ref>{{cite web |title=GVCF - Genomic Variant Call Format |url=https://gatk.broadinstitute.org/hc/en-us/articles/360035531812-GVCF-Genomic-Variant-Call-Format |website=GATK |publisher=Broad Institute}}</ref> A set of tools is also available for editing and manipulating the files.<ref>{{cite web
|url=https://vcftools.github.io/index.html|title=VCFtools from Github.io|accessdate=20 October 2016}}</ref>

==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|metadata]] describing the body of the file. Header lines are denoted as starting with {{mono|#}}. Special keywords in the header are denoted with {{mono|##}}. Recommended keywords include {{mono|fileformat}}, {{mono|fileDate}} and {{mono|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.

{| class="wikitable"
!   !! 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 [[Biology:DbSNP|dbSNP]] rs identifier, or if unknown a ".". Multiple identifiers should be separated by semi-colons without white-space.
|-
| 4 || REF     || The reference base (or bases in the case of an [[Biology:Indel|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: <code>&lt;key&gt;=&lt;data&gt;[,data]</code>.
|-
| 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)<ref name="vcf-spec"/>:
{| class="wikitable"
! Name    !! Brief description
|-
| 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
|}

== Common FORMAT fields ==
{| class="wikitable"
! Name    !! Brief description
|-
| AD || Read depth for each allele
|-
| ADF || Read depth for each allele on the forward strand
|-
| ADR || Read depth for each allele on the reverse strand
|-
| DP || Read depth
|-
| EC || Expected alternate allele counts
|-
| FT || Filter indicating if this genotype was “called”
|-
| GL || Genotype likelihoods
|-
| GP || Conditional genotype quality
|-
| GQ || Conditional genotype quality
|-
| GT || Genotype
|-
| HQ || Haplotype quality
|-
| MQ || RMS mapping quality
|-
| PL || Phred-scaled genotype likelihoods rounded to the closest integer
|-
| PQ || Phasing quality
|-
| PS || Phase set
|}
<!-- Hidden Section due to incomplete information [Illusional 02/03/2016] -->

== See also ==
* The [[Biology:FASTA format|FASTA]] format, used to represent genome sequences.
* The [[Biology:FASTQ format|FASTQ]] format, used to represent DNA sequencer reads along with quality scores.
* The [[Biology:SAM (file format)|SAM]] format, used to represent genome sequencer reads that have been aligned to genome sequences.
* The GVF format (Genome Variation Format), 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 (GA4GH) Large Scale Genomics Work Stream file format team<ref>{{Cite web|url=http://www.bio-itworld.com/2018/02/12/reliable-standards-a-necessity-for-genomic-data.aspx|title=Bio-IT World|website=www.bio-itworld.com|language=en-us|access-date=2018-10-26}}</ref>, http://ga4gh.org/#/fileformats-team

== External links ==
* [http://vcftools.sourceforge.net/VCF-poster.pdf An explanation of the format in picture form]
* {{Cite news|url = https://spectrum.ieee.org/biomedical/diagnostics/the-race-to-build-a-search-engine-for-your-dna|title = The Race to Build a Search Engine for Your DNA|last = Ossola|first = Alexandra|date = 20 March 2015|work = IEEE Spectrum|access-date = March 2015}}

==References==
{{reflist}}

{{DEFAULTSORT:}}
[[Category:Computer file formats]]
[[Category:Bioinformatics]]

{{Sourceattribution|Variant Call Format|1}}