Note: lifted from hg19
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
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 five subtracks for this track:
Four lettered subtracks, one for every nucleotide, showing
scores for mutation from the reference to that
nucleotide. All subtracks show the REVEL ensemble score on mouseover. Across the exome,
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".
In rare cases, two scores are output for the same variant at a
genome position. This happens when there are two transcripts with
different splicing patterns and since some input scores for REVEL take into account
the sequence context, the same mutation 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 different 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 mutation (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 assays, 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.
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".
REVEL scores are available at the
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
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
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/hg38/revel/a.bw stdout
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.
Thanks to the REVEL development team for providing precomputed data and fixing duplicated values in the hg38 files.
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.