Dear Biostars,

I have a gene of interest where the hypothesis is that het mutations are causative of the phenotype. Homozygous mutations are known to cause a devastating phenotype. I have a few patients with heterozygous rare, high CADD, exonic mutations that I am confident are contributory to the phenotype.

These patients have had WGS and I have their gVCF files which have been annotated with VEP including CADD/gnomad_AF etc.

I want to look at the gene's intronic regions in this cohort to make sure I've not missed anything obvious that could mean it is actually a homozygous genotype.

At present I was planning on using CADD scores and allele frequency but am aware this isn't very sophisticated.

I know much like structural variation, non-coding is a minefield of different tools and methods but wanted to get a consensus on what people are using bioinformatically to look at these regions (I have obviously read the literature but wanted a "hand-on" idea).

All the best