Description

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

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.

Display Conventions and Configuration

SpliceVarDB

According to the strength of their supporting evidence, variants were classified as "splice-altering" (~25%), "not splice-altering" (~25%), and "low-frequency splice-altering" (~50%), which correspond to weak or indeterminate evidence of spliceogenicity. 55% of the splice-altering variants in SpliceVarDB are outside the canonical splice sites (5.6% are deep intronic). The data is shown as lollipop plots that can be clicked, the details page then shows a link to SpliceVarDB with full details.

The classification thresholds primarily follow those established by the original study. However, most studies only defined criteria for splice-altering variants and did not define criteria for variants that resulted in normal splicing. The authors implemented stringent thresholds to define the normal category and ensure a high-quality set of control variants. Variants that did not meet these criteria were classified as low-frequency splice-altering variants with a wide range of sub-optimal scores. Variants that fell between the normal and splice-altering classifications were placed into a low-frequency splice-altering category. In situations where a variant was validated multiple times, if at least one validation returned splice-altering and another returned normal, the "conflicting" category was applied.

The lollipop plots are color-coded based on the score value, which corresponds to the following classifications:

• 3 - Splice-altering
• 2 - Low-frequency
• 1 - Normal
• 0 - Conflicting

Data Access

The raw data can be explored interactively with the Table Browser or the Data Integrator. The data can be accessed from scripts through our API, the track name is "splicevardb".

For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from our download server. The file for this track is called SVADB.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain only features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/splicevardb/SVADB.bb -chrom=chr21 -start=0 -end=100000000 stdout

Methods

The data was converted by Patricia Sullivan from SpliceVarDB to bigLolly format, and the UCSC Browser staff downloaded it for display.

Credits

Thanks to the SpliceVarDB team for converting the data into our data formats.

References

Sullivan PJ, Quinn JMW, Wu W, Pinese M, Cowley MJ. SpliceVarDB: A comprehensive database of experimentally validated human splicing variants. Am J Hum Genet. 2024 Oct 3;111(10):2164-2175. PMID: 39226898; PMC: PMC11480807