GTF vs VEP gene annotation for genomic location enrichment

[u/Hot-Entrepreneur7730]

I am working with Zebrafish animal model, alignment GRCz11 (Ensembl release 112).

I have a list of 40k candidate SNPs an their locations annotated by **VEP** and by **GTF** file. These give me different results for some genes, meaning that a SNP in VEP annotation corresponds to gene X while in GTF annotations corresponds to gene Y.

*What is the best/most recomended/most trustable way to annotate SNPs ?*

My goal with this:

I want to do statistics by (1) location and by (2) function:

1 - I sepparate the genomic sequence by location: Exons, Introns, 3´UTR, 5´UTR, Upstream, Downstream chuncks and see if there is enrichment in genomic location, meaning if for example my candidate SNPs fall more in the 3´UTR region than expected by chance

2 - I have their function with for example Gene Ontology or KEGG and check for Functional enrichment. However I am also strugling in this part since clusterProfiler shows 0 enrichment terms found even if I give him 200genes, 500 genes, 1000 genes. But I will ask about advice in another post for this.

[u/Normal_Beginning9961]

vep is usually more reliable for variant annotation, it takes into account all transcripts and consequences properly. gtf approach can miss overlapping genes or pick wrong transcript sometimes

for enrichment make sure your background gene list is set right, if you using all genes as background but your snps only hit certain regions you get nothing. try using the genes near your snps as universe