Non-exome variants called from whole-exome sequencing data I'm working on rather standard whole-exome sequencing data and treat it the same as whole-genome sequencing data (aligning it to the full GRCh38 reference assembly and calling variants with no exome-related parameters).

I recently noticed that my variant calling results contain numerous variants mapped to a non-exomic region, incidentally, some of them were significantly associated with the phenotype I study.

My questions are as follows:


Are the non-exome variants in my exome data invalid? or could it be that the exome kit captured more than it was designed to capture?
Should I treat raw exome sequencing data any different than genome sequencing data, and if so, what parts of my pipeline should be modified to accommodate exome data?
These are called off-targets due to unspecific binding of DNA to the capturing beads during library preparation. This is normal and expected since capturing is not a perfect process. It is correct to align against the whole genome but you should simply limit variant calling to exons (or basically the on-target regions) and ignore everything else.