DISCLAIMER: I am new and very glad to join this community, therefore I will gladly accept all answers that pointing out I have done/written something wrong/misplaced/redundant.
As first job in bioinformatics and data analysis, I'm looking for mutations occurring in some tumor samples. I have a number of tumor WES each with corresponding blood WES. When I tried to subtract blood mutations from the ones i got in the tumors, I got some hundreds of remaining variants for each blood-tumor pair. Looking deeper into this, I found out a good half of them has a gnomAD or dbSNP population frequency over 1% or more (max=26%). This is bothering me because I should be left with mostly somatic and pathogenic/rare variations, therefore I expect their frequency in the population to be very low. I ask you if you have any idea why: are my reasoning/expectation wrong? Should I check the quality of sequencing data (although it seems good)? Is this a coverage problem?
Thanks in advance! Gab