text: user9016: 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?
  
  
  user-1: 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.
  
original_text: 9016: <p>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).</p>
  
  <p>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.</p>
  
  <p>My questions are as follows:</p>
  
  <ol>
  <li>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?</li>
  <li>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?</li>
  </ol>
   -1: <p>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.</p>
  