I have a VCF file with 24 control samples and 24 treated sample all called jointly through GATK. I am not interested in the differences between all my samples vs ensembl reference used for mapping. I am interested in control vs treated. So I would like to use my control samples as reference and regenotype my treated samples against it.

To explain further, here is a simplified example:

var ref alt t1   t2   t3   c1   c2   c3
1   A   T   A/T  A/T  A/T  A/T  A/T  A/T
2   A   T   A/T  A/T  A/T  A/A  A/A  A/A
3   G   C   G/G  G/G  G/G  G/C  G/C  G/C

var1 would not be interesting as it does not differ between controls and treated. var2 and var3 are interesting.

I am thinking of an approach where I would pick variants that have identical genotypes across controls and find a consensus. Then use that as the reference and regenotype my treated samples against it. Now that brings us to an interesting question... Which allele do I pick as reference for heterozygous positions. Now sure how they do that for all the reference genomes...

In this example, I am just going to pick the most common allele for each variant and set that as the reference. var1 was skipped earlier and the new reference looks like:

var ref
2   A
3   G

Now if we regenotype the treated samples against the new reference, we get:

var ref alt c1   c2   c3
2   A   A   A/A  A/A  A/A
3   G   C   G/C  G/C  G/C

var 2 can be skipped because it is not polymorphic anymore (only because A was chosen as ref). Then we have:

var ref alt c1   c2   c3
3   G   C   G/C  G/C  G/C

Is this correct? Anything like this implemented in any workflow/software? Ultimately the aim is to pick only differences caused due to the experimental condition.