Hi all,
I have some lof variants and I want to know if they have already been detected in GNOMAD (I am essentially curious if my lof variants are novel).
In order to make this comparison to GNOMAD I have run my variants through LOFTEE and am getting some surprising results. The vast majority of my variants are marked as low confidence because they did not pass the NON_CAN_SPLICE_SURR filter. With that said I have found variants on GNOMAD that are HC that are almost in the same position, and on the same transcript.
So does GNOMAD use the NON_CAN_SPLICE_SURR filter?
For example, from my data I have the following frameshift variant:
7:140373880-140373881 (GA/-) (ENST00000072869)
IMPACT=HIGH;STRAND=1;LoF=LC;LoF_filter=NON_CAN_SPLICE_SURR;...
While in GNOMAD there is a frameshift variant on the same gene right next to it that does not have that same LoF_filter, and is marked as high confidence:
7-140373879-TGA-T https://gnomad.broadinstitute.org/variant/7-140373879-TGA-T?dataset=gnomad_r2_1
Furthermore, after looking at the GNOMAD flagship paper Extended Data Figure 5, there is no mention of the NON_CAN_SPLICE_SURR filter.
Any help clarifying this up is appreciated :)
Does anyone have any idea what tags I could use to get the GNOMAD people to see this post?
Moving forward I have just used the 9 LOFTEE filters listed in the flagship paper to subset my VEP results. I will use these to make my comparisons to GNOMAD.
Can you post the commands you used?
I am having some issues running that plugin on vep v110. It appears in fields but it doesn't annotate it.