REVEL Scores Track Settings
 
REVEL Pathegenicity Score for single-base coding mutations (zoom for exact score)   (All Phenotype and Literature tracks)

Display mode:       Reset to defaults

Type of graph:
Track height: pixels (range: 8 to 128)
Data view scaling: Always include zero: 
Vertical viewing range: min:  max:   (range: 0 to 1)
Transform function:Transform data points by: 
Windowing function: Smoothing window:  pixels
Negate values:
Draw y indicator lines:at y = 0.0:    at y =
Graph configuration help
List subtracks: only selected/visible    all  
hide
 Configure
 Mutation: A  Revel: Mutation is A   Schema 
hide
 Configure
 Mutation: C  Revel: Mutation is C   Schema 
hide
 Configure
 Mutation: G  Revel: Mutation is G   Schema 
hide
 Configure
 Mutation: T  Revel: Mutation is T   Schema 
Related tracks
  • CADD: CADD, a similar deleteriousness score, and not used as an input by REVEL
Source data version: Version 1, Feb 5th 2020


new Note: Released by UCSC June 24, 2021

Description

This track collection shows Rare Exome Variant Ensemble Learner (REVEL) scores for predicting the deleteriousness of each nucleotide change in the genome.

REVEL is an ensemble method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. REVEL was trained using recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing.

Most authors of deleteriousness scores argue against using fixed cutoffs in diagnostics. But to give an idea of the meaning of the score value, the REVEL authors note: "For example, 75.4% of disease mutations but only 10.9% of neutral variants (and 12.4% of all ESVs) have a REVEL score above 0.5, corresponding to a sensitivity of 0.754 and specificity of 0.891. Selecting a more stringent REVEL score threshold of 0.75 would result in higher specificity but lower sensitivity, with 52.1% of disease mutations, 3.3% of neutral variants, and 4.1% of all ESVs being classified as pathogenic". (Figure S1 of the reference below)

Display Conventions and Configuration

There are four subtracks for this track: one for every nucleotide showing a score for the mutation represented by a mutation from the reference to that nucleotide. All subtracks show the REVEL ensemble score on mouseover, representing each of the possible ~9 billion SNVs in the genome. The score is an aggregation of the outputs of the 13 tools.

For single nucleotide variants (SNV), at every genome position, there are three values per position, one for every possible nucleotide mutation. The fourth value, "no mutation", representing the reference allele, e.g. A to A, is always set to zero, "0.0". REVEL only takes into account amino acid changes, so a nucleotide change that results in no amino acid change (synonymous) also receives the score "0.0".

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.

For hg38, note that the data was 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 allele 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 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. 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 whole 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/hg19/revel/a.bw stdout

Methods

Data were converted from the files provided on the REVEL Downloads website. As with all other tracks, a full log of all commands used for the conversion is available in our source repository, for hg19 and hg38. The release used for each assembly is shown on the track description page.

Credits

Thanks to the REVEL development team for providing precomputed data and fixing duplicated values in the hg38 files.

References

Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, Musolf A, Li Q, Holzinger E, Karyadi D, et al. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants Am J Hum Genet. 2016 Oct 6;99(4):877-885. PMID: 27666373; PMC: PMC5065685