9233f89064f6e7154715cd0c4c893a3208b88b45 jnavarr5 Tue Jun 24 17:07:16 2025 -0700 Making changes from code review. Adding missing commas and moving the 19 lifted icon, refs #35968 diff --git src/hg/makeDb/trackDb/human/revel.html src/hg/makeDb/trackDb/human/revel.html index 6a9c51d528c..861cd0f6d0a 100644 --- src/hg/makeDb/trackDb/human/revel.html +++ src/hg/makeDb/trackDb/human/revel.html @@ -47,51 +47,51 @@ the sequence context, the same variant can get two different scores. In these cases, only the maximum score is shown in the four per-nucleotide subtracks. The complete set of scores are shown in the Overlaps track.

One subtrack, Overlaps, shows alternate REVEL scores when applicable. In rare cases (0.05% of genome positions), multiple scores exist with a single variant, due to multiple, overlapping transcripts. For example, if there are two transcripts and one covers only half of an exon, then the amino acids that overlap both transcripts will get two distinct REVEL scores, since some of the underlying scores (polyPhen for example) take into account the amino acid sequence context and this context is different depending on the transcript. For these cases, this subtrack contains at least two graphical features, for each affected genome position. Each feature is labeled -with the reference or variant (A, C, T or G). The transcript IDs and resulting score is +with the reference or variant (A, C, T, or G). The transcript IDs and resulting score is shown when hovering over the feature or clicking it. For the large majority of the genome, this subtrack has no features. This is because REVEL usually outputs only a single score per nucleotide and most transcript-derived amino acid sequence contexts are identical.

Note that in most diagnostic testing scenarios, variants are called using WGS pipelines, not RNA-seq. As a result, variants are originally located on the genome, not on transcripts, and the choice of transcript is made by a variant calling software using a heuristic. In addition, clinically, in the field, some transcripts have been agreed-on as more relevant for a disease, e.g. because only certain transcripts may be expressed in the relevant tissue. So the choice of the most relevant transcript, and as such the REVEL score, may be a question of manual curation standards rather than a result of the variant itself.

Note further that these thresholds represent the recommended score cutoffs for genes with no Variant Curation Expert Panel (VCEP) rules. For genes with published VCEP rules, the VCEP might -select different thresholds which are adjusted for the frequency of the +select different thresholds, which are adjusted for the frequency of the relevant disorders. These are available in the ClinGen Criteria Specification.

When using this track, zoom in until you can see every basepair at the top of the display. Otherwise, there are several nucleotides per pixel under your mouse cursor and no score will be shown on the mouseover tooltip.

Track colors

This track is colored according to Table 2 in Pejaver et al. The colors represent the recommended ClinGen score cutoffs. @@ -117,59 +117,59 @@

More details on these scoring ranges can be found in Bergquist et al. Genet Med 2025, Table 2:

Table 2 from Bergquist Genet Med 2025

For hg38, note that the data were converted from the hg19 data using the UCSC liftOver program, by the REVEL authors. This can lead to missing values or duplicated values. When a hg38 position is annotated with two scores due to the lifting, the authors removed all the scores for this position. They did the same when the reference nucleotide has changed from hg19 to hg38. Also, on hg38, the track has -the "lifted" icon to indicate -this . You can double-check if a nucleotide +the "lifted" icon to indicate +this. You can double-check if a nucleotide position is possibly affected by the lifting procedure by activating the track "Hg19 Mapping" under "Mapping and Sequencing".

Data access

REVEL scores are available at the REVEL website. The site provides precomputed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants among the large number of rare variants discovered in sequencing studies.

The REVEL data on the UCSC Genome Browser can be explored interactively with the Table Browser or the Data Integrator. The previous overlap bigBed version file is available in the archives of our downloads server. For automated download and analysis, the genome annotation is stored at UCSC in bigWig files that can be downloaded from our download server. The files for this track are called a.bw, c.bw, g.bw, t.bw. Individual -regions or the genome annotation can be obtained using our tool bigWigToWig +regions or the genome annotation can be obtained using our tool bigWigToWig, 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 tools can also be used to obtain features confined to given range, e.g.

bigWigToBedGraph -chrom=chr1 -start=100000 -end=100500 http://hgdownload.soe.ucsc.edu/gbdb/$db/revel/a.bw stdout

Methods

Data were converted from the files provided on the REVEL Downloads website. As with all other tracks,