The "Splicing Impact" container track contains tracks showing the predicted or validated effect of variants close to splice sites.

AbSplice

AbSplice is a method that predicts aberrant splicing across human tissues, as described in Wagner, Çelik et al., 2023. This track displays precomputed AbSplice scores for all possible single-nucleotide variants genome-wide. The scores represent the probability that a given variant causes aberrant splicing in a given tissue. AbSplice scores can be computed from VCF files and are based on quantitative tissue-specific splice site annotations (SpliceMaps). While SpliceMaps can be generated for any tissue of interest from a cohort of RNA-seq samples, this track includes 49 tissues available from the Genotype-Tissue Expression (GTEx) dataset.

SpliceAI Variants

SpliceAI is an open-source deep learning splicing prediction algorithm that can predict splicing alterations caused by DNA variations. To score variants, the spliceAI algorithm is run on the genome sequence itself and scores each nucleotide for the probability that it is a donor or acceptor site, on both the forward and the reverse strand. Then variants are added to the sequence and the new sequence is scored. Variants may activate nearby cryptic splice sites, leading to abnormal transcript isoforms. SpliceAI was developed at Illumina; a lookup tool is provided by the Broad institute.

SpliceAI Wildtype

This SpliceAI "Wildtype" container track shows the scores for the genome sequence itself, without variants, from predicted splice donor (5' intron boundaries) and splice acceptor (3' intron boundaries) sites. Predictions are strand-specific, with separate subtracks for the plus and minus strands. These tracks are useful in combination with the variants track for evaluating new transcript models. They can be used to assess potential exon boundaries or possible splice acceptor sites.

SpliceAI only annotates variants within genes defined by the gene annotation file. Additionally, SpliceAI does not annotate variants if they are close to chromosome ends (5kb on either side), deletions of length greater than twice the input parameter -D, or inconsistent with the reference fasta file.

The unmasked tracks include splicing changes corresponding to strengthening annotated splice sites and weakening unannotated splice sites, which are typically much less pathogenic than weakening annotated splice sites and strengthening unannotated splice sites. The delta scores of such splicing changes are set to 0 in the masked files. We recommend using the unmasked tracks for alternative splicing analysis and masked tracks for variant interpretation.

SpliceVarDB

SpliceVarDB is an online database consolidating over 50,000 variants assayed for their effects on splicing in over 8,000 human genes. The authors evaluated over 500 published data sources and established a spliceogenicity scale to standardize, harmonize, and consolidate variant validation data generated by a range of experimental protocols. Genes and variant locations were obtained using GENCODE v44. Splice regions were calculated as specific distances from the closest canonical exon, including 5' and 3' untranslated regions (UTRs). The database is available at splicevardb.org.

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