Gene that CTX hits the intron must be broken in the midst of its coding frame (exon continuation is broken) therefore PREDICTED_LOF should be justified for that matter. If both breakpoints were in the intergenic region then PREDICTED_LOF assessment might have been problematic.

Thanks for the response and clarifying that.
The breakpoints are not overlapping at any exon (one bp is intergenic, the other is in intronic site).
I still don't see how so many genes have been computed under PREDCITED_LOF.

Hi @Nehir291, please refer to the SVAnnotate tool documentation for definitions of each annotation: https://gatk.broadinstitute.org/hc/en-us/articles/21905053774363-SVAnnotate. For translocations, PREDICTED_LOF is assigned if a breakpoint falls at any point in the transcript, so an intronic breakpoint would still be annotated as PREDICTED_LOF for any impacted genes. This is because only part of the gene exists on each chromosome after the translocation, which is likely to result in a truncated transcript subject to nonsense-mediated decay.

Perhaps in some cases this definition is overly permissive, such as if only the UTR or one shorter exon is removed by the translocation - those cases could be worth revisiting.

I hope this helps explain the behavior you are seeing. If this does not fully explain all the PREDICTED_LOF annotations you are observing, please share the CTX breakpoints, the annotations, the SVAnnotate version, and the GTF used so we can investigate further.