Method to merge two vcf files that don't have same alt information

Question

[Apprentice]

Hi

I have two vcf files that file names are A.vcf and B.vcf.

A.vcf

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CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SampleB SampleA chr1 762560 SNV_1 G T . . . GT:AD:DP:RGQ 0/0:31,0:31:81:0,81,1215 0/1:18,12:30:99:375,0,544

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B.vcf

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CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SampleB SampleA chr1 762560 SNV_2 G . . . . GT:DP:RGQ 0/0:19:51 0/0:23:63

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As you see above, SNV_1 in A.vcf and SNV_2 in B.vcf are SNVs on the same position. However SNV_1 has Alt info "T", but SNV_2 doesn't have Alt info. Thus, SNV_2 in B.vcf doesn't have AD info in genotype data.

I would like to know how to merge these two vcf files into one vcf file, recognizing SNV_A and SNV_B as same variant data.

Could you give me any advice?

Answer 1

[Vivek]

You would likely just retain the alternate allele as T in the merged VCF and the genotype for samples in B.vcf will be 0/0 as both samples are shown to be homozygous reference for this locus. As long as both VCFs are generated with respect to the same reference genome you'll be fine.

[Apprentice]

Hi Vivek! Thank you for your quick reply. I made a mistake about sample name in B.vcf.

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Correct B.vcf is as below: CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SampleC SampleD chr1 762560 SNV_2 G . . . . GT:DP:RGQ 0/0:19:51 0/0:23:63

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So I merge two files with different alt allele and different sample. Could you give me any advice?

[Vivek]

It seems like there is no alt allele in B.vcf since both samples, C & D appear to be homozygous reference.

If you are worried about convention, you should try merging them with something like GATK's combine variants module and see how that goes.

[Apprentice]

Thank you for your advice.

I'll try it

[Apprentice]

Using GATK's combine variants, I could merged vcf files that don't have same alt information. Thank you for your help!