Most frequent targets of splice site mutations are the consensus GT and AG donor and acceptor dinucleotides respectively.
As it has been also observed in T. brucei, the second most frequent dinucleotide at splice site is GG.
This suggests that coding SNVs as well as SNVs in UTRs and in splice sites are more frequent in genes that display differential expression or alternative splicing.
Cryptic acceptor splice sites are more frequent in exons than in introns, likely due to depletion of AG dinucleotides upstream of the original acceptor sites [ 32].
In some clinics, patients are routinely tested for one relatively frequent IVS14+1G>A splice-site polymorphism [ 52].
By contrast, the 3′ of the gene, which encodes several domains implicated in transcriptional activation and response to cell signaling, shows a remarkably active evolutionary history, with diverse isoforms and frequent creation and loss of new exons and splice sites.
These data suggest that the apparently benign nature of antisense intronic insertions and the presence of functional antisense splice sites can lead to the frequent exonization of L1 sequences, as we have observed in our dataset.
Mutations at the completely conserved guanine at the intronic + 1 position (Fig. 1A, top) of donor splice sites (5'ss), a relatively frequent cause of severe human genetic diseases [4], are also generally considered null mutations as they are predicted to disrupt the splicing process [5].
Among the five most common AS types, alternative 3' splice sites type (A3) was the most frequent in A. thaliana and C. elegans, but exon skipping (ES) was the most frequent in D. melanogaster, M. musculus and H. sapiens.
In addition, we observed that IR is the most common event and the use of alternative 3′ splice sites is more than two-fold more frequent than the use of alternative 5′ splice sites.
