Variant classification
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Introduction
The Variant Call Format (VCF) is a flexible file format specification that allows us to represent many different variant types ranging from SNPs, indels to copy number variations. However, variant representation in VCF is non-unique for variants that have explicitly expressed reference and alternate sequences.
On this wiki page, we describe a a variant classification system for VCF variants.
Definitions
The definition of a variant is based on the definition of each allele with respect to the reference sequence. We consider 5 major types as follows.
- 1. SNP
- The reference and alternate sequences are of length 1 and the base nucleotide is different from one another.
- 2. MNP
- a.The reference and alternate sequences are of the same length and have to be greater than 1 and all nucleotides in the sequences differ from one another.
- OR
- b. all reference and alternate sequences have the same length.
- 3. INDEL
- a. The reference and alternate sequence are not the same length.
- AND
- b. The removal of a subsequence of the longer sequence would reduce the longer sequence to the smaller sequence.
- 4. CLUMPED
- 5. SV
- The alternate sequence is represented by a angled bracket tag.
Examples
We present the following examples to explain the concepts explained earlier.
Simple Biallelic Examples
SNP
REF A ALT G
MNP
REF AT ALT GC
INDEL
REF AT ALT A
SV
REF A ALT <DEL>
Complex Biallelic Examples
SNP|INDEL
REF AT ALT G
MNP|INDEL
REF ATT ALT GC
MNP|CLUMPED
REF ATTTT ALT GTTTC #since all the alleles are of the sample length, classified as MNP too.
INDEL|CLUMPED
REF ATTTTTTTT ALT GTTTC
Simple Multiallelic Examples
SNP
REF A ALT G ALT C
MNP
REF AG ALT GC ALT CT
INDEL
REF ATTT ALT ATT ALT AT
Complex Multiallelic Examples
SNP|MNP
REF AT ALT GT #SNP ALT AC #SNP #since all the alleles are of the sample length, classified as MNP too.
MNP|CLUMPED
REF ATTTG ALT GTTTC #CLUMPED ALT ATTTC #CLUMPED #since all the alleles are of the sample length, classified as MNP too.
SNP|MNP|INDEL
REF GT ALT CT #SNP ALT AG #MNP ALT GTT #INDEL
SNP|MNP|INDEL|CLUMPED
REF GTTT ALT CG #MNP|INDEL ALT AG #MNP ALT GTGTG #SNP|INDEL|CLUMPED
SV Examples
======= Structural variants ========
no. of structural variants : 41217
2 alleles : 38079
deletion : 13135 <DEL>
insertion : 16451 <INS>
mobile element : 16253 <INS:ME>
ALU : 12513 <INS:ME:ALU>
LINE1 : 2911 <INS:ME:LINE1>
SVA : 829 <INS:ME:SVA>
numt : 198 <INS:MT>
duplication : 664 <DUP>
inversion : 100 <INV>
copy number variation : 7729 <CN4>
>=3 alleles : 3138
copy number variation : 3138 <CN4>,<CN8>
Output
Summarizes the variants in a VCF file
#summarizes the variants found in mills.vcf vt peek mills.vcf
usage : vt peek [options] <in.vcf>
options : -o output VCF file [-]
-I file containing list of intervals []
-i intervals []
-r reference sequence fasta file []
-- ignores the rest of the labeled arguments following this flag
-h displays help
#This is a sample output of a peek command which summarizes the variants found in a VCF file.
stats: no. of samples : 0
no. of chromosomes : 22
========== Micro variants ==========
no. of SNPs : 77228885
2 alleles (ts/tv) : 77011302 (2.11) [52287790/24723512]
3 alleles (ts/tv) : 216560 (0.75) [185520/247600]
4 alleles (ts/tv) : 1023 (0.50) [1023/2046]
no. of MNPs : 0
2 alleles (ts/tv) : 0 (-nan) [0/0]
>=3 alleles (ts/tv) : 0 (-nan) [0/0]
no. Indels : 2147564
2 alleles (ins/del) : 2124842 (0.47) [683250/1441592]
>=3 alleles (ins/del) : 22722 (2.12) [32411/15286]
no. SNP/MNP : 0
3 alleles (ts/tv) : 0 (-nan) [0/0]
>=4 alleles (ts/tv) : 0 (-nan) [0/0]
no. SNP/Indels : 12913
2 alleles (ts/tv) (ins/del) : 412 (0.41) [120/292] (3.68) [324/88]
>=3 alleles (ts/tv) (ins/del) : 12501 (0.43) [7670/17649] (18.64) [12434/667]
no. MNP/Indels : 153
2 alleles (ts/tv) (ins/del) : 0 (-nan) [0/0] (-nan) [0/0]
>=3 alleles (ts/tv) (ins/del) : 153 (0.30) [138/465] (0.27) [67/248]
no. SNP/MNP/Indels : 2
3 alleles (ts/tv) (ins/del) : 0 (-nan) [0/0] (-nan) [0/0]
4 alleles (ts/tv) (ins/del) : 2 (0.00) [3/5] (1.00) [3/3]
>=5 alleles (ts/tv) (ins/del) : 0 (-nan) [0/0] (-nan) [0/0]
no. of clumped variants : 19025
2 alleles : 0 (-nan) [0/0] (-nan) [0/0]
3 alleles : 18508 (0.16) [12152/75366] (0.00) [93/18653]
4 alleles : 451 (0.15) [369/2390] (0.33) [201/609]
>=5 alleles : 66 (0.09) [37/414] (1.19) [107/90]
====== Other useful categories =====
no. complex variants : 32093
2 alleles (ts/tv) (ins/del) : 412 (0.41) [120/292] (3.68) [324/88]
>=3 alleles (ts/tv) (ins/del) : 31681 (0.21) [20369/96289] (0.64) [12905/20270]
======= Structural variants ========
no. of structural variants : 41217
2 alleles : 38079
deletion : 13135
insertion : 16451
mobile element : 16253
ALU : 12513
LINE1 : 2911
SVA : 829
numt : 198
duplication : 664
inversion : 100
copy number variation : 7729
>=3 alleles : 3138
copy number variation : 3138
========= General summary ==========
no. of reference : 0
no. of observed variants : 79449759
no. of unclassified variants : 0
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This page is maintained by Adrian.
