Description
NOTE:
ClinVar is intended for use primarily by physicians and other
professionals concerned with genetic disorders, by genetics researchers, and
by advanced students in science and medicine. Research data is not easy to interpret, and not
everything shown is necessarily useful. While the ClinVar
database is open to all academic users, users seeking information about a
personal medical or genetic condition are urged to consult with a qualified
physician for diagnosis and for answers to personal questions.
These tracks show the genomic positions of variants in the
ClinVar database.
ClinVar is a free, public archive of reports
of the relationships among human variations and phenotypes, with supporting
evidence.
The ClinVar SNVs track displays substitutions and indels shorter than 50 bp, and
the ClinVar CNVs track displays copy number variants (CNVs) equal to or larger than 50 bp.
The ClinVar Interpretations track displays the genomic positions of individual variant
submissions and interpretations of the clinical significance and their relationship to disease in
the ClinVar database.
Note on the start position of variants: The data in the track are obtained directly from ClinVar's FTP site.
We display the data obtained from ClinVar as-is to avoid discrepancies between UCSC and NCBI.
However, be aware that the ClinVar conventions are different from the VCF standard.
Variants may be right-aligned or may contain additional context, e.g. for
inserts. The VCF position is also available in this track,
as an additional field, at the end of the list of fields, when you click any variant.
It can be extracted using our table browser, the API,
or the bigBedToBed tool (see the Data access section below).
And GnomAD has a converter.
Display Conventions and Configuration
Items can be filtered according to the size of the variant, variant type, clinical significance,
allele origin, phenotype, and molecular consequence, using the track Configure options.
Each subtrack has separate display controls, as described
here.
Entries in the ClinVar SNVs and ClinVar Interpretations tracks are colored by clinical
significance:
- red for pathogenic
- dark blue for variant of uncertain significance
- green for benign
- dark grey for not provided
- light blue for conflicting
Entries in the ClinVar CNVs track are colored by type of variant, among others:
- red for loss
- blue for gain
- purple for inversion
- orange for insertion
A light-to-dark color gradient indicates the clinical significance of each variant, with the
lightest shade being benign to the darkest shade being pathogenic. Detailed information on the
CNV color code is described
here.
In the ClinVar SNV track, an option to show triangles for protein-truncating mutations is available
under the Decoration settings, using the Glyph decoration placement option. Triangles can be placed
using either the Overlay or Adjacent display. Variants with the following molecular consequences
are considered protein-truncating: nonsense, frameshift variant, splice acceptor variant, and
splice donor variant.
Mouseover on the genomic locations of ClinVar variants shows variant details, clinical
interpretation, and associated conditions. Further information on each variant is displayed on
the details page by clicking onto any variant. ClinVar is an archive for assertions of clinical
significance made by the submitters. The level of review supporting the assertion of clinical
significance for the variation is reported as the
review status.
Stars (0 to 4) provide a graphical representation of the aggregate review status.
The variants in the ClinVar Interpretations track are arranged from top to bottom by the variant
classification of each submission:
- P: Pathogenic
- LP: Likely Pathogenic
- VUS: Variant of Unknown Significance
- LB: Likely Benign
- B: Benign
- OTH: Others
The size of the bead represents
the number of submissions at that genomic position. For better readability, the numbers
are binned into three categories:
- Small-sized beads: 1-2 submissions
- Medium-sized beads: 3-7 submissions
- Large-sized beads: 8 or more submissions
Hovering on the track items shows the genomic variations that start at that position
and the number of individual submissions with that classification. The details page lists all
rated submissions from ClinVar, with specific details to the interpretation of the clinical or
functional significance of each variant in relation to a condition. Interpretation is at
the variant-level, not at the case (or patient-specific) level.
More information about using and understanding the ClinVar data can be found
here.
For the human genome version hg19, the hg19 genome released by UCSC in 2009 had a
mitochondrial genome "chrM" that was not the same as the one later used for most
databases like ClinVar. As a result, we added the official mitochondrial genome
in 2020 as "chrMT", and all mitochondrial annotations of ClinVar and most other
databases are shown on the mitochondrial genome called "chrMT". For a full description
of the issue of the mitochondrial genome in hg19, please see the
hg19 README file
on our download site.
Data updates
ClinVar publishes a new release on the
first Thursday of every month.
This track is then updated automatically at most six days
later. The exact date of our last update is shown on the track configuration page.
You can find the previous versions of the track organized by month on our
downloads server in the
archive
directory. To display one of these previous versions, paste the URL to one of
the older files into the custom track text input field under "My Data > Custom Tracks".
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 names are
"clinVarMain and "clinVarCnv".
For automated download and analysis, the genome annotation is stored in a bigBed file that
can be downloaded from
our download server.
The files for this track are called clinvarMain.bb and clinvarCnv.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/bbi/clinvar/clinvarMain.bb -chrom=chr21 -start=0 -end=100000000 stdout
Methods
ClinVar files were reformatted at UCSC to the bigBed format.
The data is updated every month, one week after the ClinVar release date.
The program that performs the update is available on
GitHub.
Credits
Thanks to NCBI for making the ClinVar data available on their FTP site as a tab-separated file.
If you email them (clinvar@ncbi.nlm.nih.gov), feel free to CC us, it is always good to learn more about ClinVar.
References
Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J
et al.
ClinVar: public archive of interpretations of clinically relevant variants.
Nucleic Acids Res. 2016 Jan 4;44(D1):D862-8.
PMID: 26582918; PMC: PMC4702865
Azzariti DR, Riggs ER, Niehaus A, Rodriguez LL, Ramos EM, Kattman B, Landrum MJ, Martin CL, Rehm HL.
Points to consider for sharing variant-level information from clinical genetic testing with
ClinVar.
Cold Spring Harb Mol Case Stud. 2018 Feb;4(1).
PMID: 29437798; PMC: PMC5793773
|