Variant Call Format

File format for genomic variation data From Wikipedia, the free encyclopedia

The Variant Call Format or VCF is a standard text file format used in bioinformatics for storing gene sequence or DNA sequence variations. The format was developed in 2010 for the 1000 Genomes Project and has since been used by other large-scale genotyping and DNA sequencing projects.[1][2] VCF is a common output format for variant calling programs due to its relative simplicity and scalability.[3][4] Many tools have been developed for editing and manipulating VCF files, including VCFtools, which was released in conjunction with the VCF format in 2011, and BCFtools, which was included as part of SAMtools until being split into an independent package in 2014.[1][5]

Quick Facts Filename extension, Developed by ...
Variant Call Format
Filename extension
.vcf
Developed by1000 Genomes Project
Latest release
4.5
October 9, 2024; 6 months ago (2024-10-09)
Type of formatBioinformatics
Extended fromTab-separated values
Extended togVCF
Open format?Yes
Websitesamtools.github.io/hts-specs/VCFv4.5.pdf
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The standard is currently in version 4.5,[6][7] although the 1000 Genomes Project has developed its own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.[8]

Additional file formats have been developed based on VCF, including genomic VCF (gVCF). gVCF is an extended format which includes additional information about "blocks" that match the reference and their qualities.[9][10]

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
Thumb
Demonstrating the difference between the binary BCF and VCF formats.

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

Summarize
Perspective

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.

More information Name, Brief description (see the specification for details). ...
NameBrief description (see the specification for details).
1CHROMThe 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.
2POSThe 1-based position of the variation on the given sequence.
3IDThe identifier of the variation, e.g. a dbSNP rs identifier, or if unknown a ".". Multiple identifiers should be separated by semi-colons without white-space.
4REFThe reference base (or bases in the case of an indel) at the given position on the given reference sequence.
5ALTThe list of alternative alleles at this position.
6QUALA quality score associated with the inference of the given alleles.
7FILTERA flag indicating which of a given set of filters the variation has failed or PASS if all the filters were passed successfully.
8INFO    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>[,data].
9FORMATAn (optional) extensible list of fields for describing the samples. See below for some common fields.
+SAMPLEsFor each (optional) sample described in the file, values are given for the fields listed in FORMAT
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Common INFO fields

Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional):[6]

More information Name, Brief description ...
NameBrief description
AAancestral allele
ACallele count in genotypes, for each ALT allele, in the same order as listed
AFallele frequency for each ALT allele in the same order as listed (use this when estimated from primary data, not called genotypes)
ANtotal number of alleles in called genotypes
BQRMS base quality at this position
CIGARcigar string describing how to align an alternate allele to the reference allele
DBdbSNP membership
DPcombined depth across samples, e.g. DP=154
ENDend position of the variant described in this record (for use with symbolic alleles)
H2membership in hapmap2
H3membership in hapmap3
MQRMS mapping quality, e.g. MQ=52
MQ0Number of MAPQ == 0 reads covering this record
NSNumber of samples with data
SBstrand bias at this position
SOMATICindicates that the record is a somatic mutation, for cancer genomics
VALIDATEDvalidated by follow-up experiment
1000Gmembership in 1000 Genomes
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Any other info fields are defined in the .vcf header.

Common FORMAT fields

More information Name, Brief description ...
NameBrief description
ADRead depth for each allele
ADFRead depth for each allele on the forward strand
ADRRead depth for each allele on the reverse strand
DPRead depth
ECExpected alternate allele counts
FTFilter indicating if this genotype was “called”
GLGenotype likelihoods
GPGenotype posterior probabilities
GQConditional genotype quality
GTGenotype
HQHaplotype quality
MQRMS mapping quality
PLPhred-scaled genotype likelihoods rounded to the closest integer
PQPhasing quality
PSPhase set
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Any other format fields are defined in the .vcf header.

Binary VCF

Binary VCF or BCF files are binary, BGZF compressed variation of VCF files. BCF files allow fast and efficient indexed queries through tools like Tabix once an index file has been created.

See also

  • The FASTA format, used to represent genome sequences.
  • The FASTQ format, used to represent DNA sequencer reads along with quality scores.
  • The 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.

References

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