22d0df7a78276cdebe8cf0cc5f46cc0498e78738 abenetpa Tue Oct 20 01:06:12 2020 -0700 added reference to desc page #26330 diff --git src/hg/makeDb/trackDb/human/clinvar.html src/hg/makeDb/trackDb/human/clinvar.html index ff5b936..c65bc19 100644 --- src/hg/makeDb/trackDb/human/clinvar.html +++ src/hg/makeDb/trackDb/human/clinvar.html @@ -1,174 +1,185 @@ <h2>Description</h2> <div class="warn-note" style="border: 2px solid #9e5900; padding: 5px 20px; background-color: #ffe9cc;"> <p><span style="font-weight: bold; color: #c70000;">NOTE:</span><br> 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. 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.</p> </div> <p> These tracks show the genomic positions of variants in the <a href="https://www.ncbi.nlm.nih.gov/clinvar/" target="_blank">ClinVar database</a>. ClinVar is a free, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence. </p> <p> The <b>ClinVar SNVs track</b> displays substitutions and indels shorter than 50 bp and the <b>ClinVar CNVs track</b> displays copy number variants (CNVs) equal or larger than 50 bp. Until October 2017, all variants with the ClinVar types <em>copy number gain/loss</em> and <em>DbVar "nsv" accessions</em> were assigned in the CNV category. Because the ClinVar type no longer captures this information, any variation equal to or larger than 50 bp is now considered a CNV. </p> <p> The <b>ClinVar Interpretations track</b> displays the genomic positions of individual variant submissions and interpretations of the clinical significance and their relationship to disease in the ClinVar database. </p> <p> <b>Note:</b> 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. ExAC/gnomAD make available <a href="https://github.com/macarthur-lab/clinvar" target="_blank">a converter</a> to make ClinVar more comparable to VCF files.</p> <h2>Display Conventions and Configuration</h2> <p> Items can be filtered according to the size of the variant, variant type, clinical significance, allele origin, and molecular consequence, using the track <b>Configure</b> options. Each subtrack has separate display controls, as described <a href="../../goldenPath/help/multiView.html">here</a>. </p> <p> <b>Mouseover</b> 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 a click 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 <a target="_blank" href="https://www.ncbi.nlm.nih.gov/clinvar/docs/review_status/">review status</a>. <b>Stars</b> (0 to 4) provide a graphical representation of the aggregate review status. </p> <p> Entries in the <b>ClinVar CNVs track</b> are colored by <b>type of variant</b>, among others: <ul> <li><b><font color="red">red for loss</font></b></li> <li><b><font color="blue">blue for gain</font></b></li> <li><b><font color="purple">purple for inversion</font></b></li> <li><b><font color="orange">orange for insertion</font></b></li> </ul> A light-to-dark color gradient indicates the <b>clinical significance</b> of each variant, with the lightest shade being benign, to the darkest shade being pathogenic. Detailed information on the CNV color code is described <a href="../../goldenPath/help/hgCnvColoring.html">here</a>. </p> <p> Entries in the <b>ClinVar SNVs and ClinVar Interpretations tracks</b> are colored by <b>clinical significance</b>: <ul> <li><b><font color="d20000">red for pathogenic</font></b></li> <li><b><font color="000088">dark blue for variant of uncertain significance</font></b></li> <li><B><font color="#00d200">green for benign</font></b></li> <li><B><font color="#888">dark grey for not provided</font></b></li> <li><B><font color="#8979D4">light blue for conflicting</font></b></li> </ul> </p> <p> The variants in the <b>ClinVar Interpretations track</b> are sorted 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. Hovering on the track items shows the genomic variations which 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 variant-level, not at case (or patient-specific) level. </p> <p> More information about using and understanding the ClinVar data can be found <a target="_blank" href="https://www.ncbi.nlm.nih.gov/clinvar/docs/faq/">here</a>. </p> <p> 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 full description of the issue of the mitochondrial genome in hg19, please see the <a target=_blank href="https://hgdownload.soe.ucsc.edu/goldenPath/hg19/bigZips/">README file</a> on our download site. </p> <h2>Data updates</h2> <p>ClinVar publishes a new release on the <a href="https://www.ncbi.nlm.nih.gov/feed/rss.cgi?ChanKey=ClinVarNews">first Thursday every month</a> and this track is updated automatically at most six days later. The exact date of our last update is shown when you click onto any variant. You can find the previous versions of the track organized by month on our downloads server in the <a href="http://hgdownload.soe.ucsc.edu/goldenPath/hg19/archive/clinvar/" target="_blank">archive</a> directory. To access one of these previous versions, paste the URL to one of the older files into our "Custom tracks" box.</p> <H2>Data access</H2> <p> The raw data can be explored interactively with the <a href="../cgi-bin/hgTables">Table Browser</a> or the <a href="../cgi-bin/hgIntegrator">Data Integrator</a>. The data can be accessed from scripts through our <a href="https://api.genome.ucsc.edu">API</a>, the track names are "clinVarMain and "clinVarCnv". <p> For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from <a href="http://hgdownload.soe.ucsc.edu/gbdb/$db/bbi/" target="_blank">our download server</a>. The files for this track are called <tt>clinVarMain.bb</tt> and <tt>clinVarCnv.bb</tt>. Individual regions or the whole genome annotation can be obtained using our tool <tt>bigBedToBed</tt> 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 <a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads">here</a>. The tool can also be used to obtain only features within a given range, e.g. <tt>bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg19/bbi/clinvar/clinvarMain.bb -chrom=chr21 -start=0 -end=100000000 stdout</tt></p> </p> <h2>Methods</h2> <p> ClinVar files were reformatted at UCSC to the <a href="../goldenPath/help/bigBed.html">bigBed</a> format. The data is updated every month, one week after the ClinVar release date. The program that performs the update is available on <a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/utils/otto/clinvar/clinVarToBed" target="_blank">Github</a>. </p> <h2>Credits</h2> <p> Thanks to NCBI for making the ClinVar data available on their FTP site as a tab-separated file. </p> <h2>References</h2> <p> Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J <em>et al</em>. <a href="https://academic.oup.com/nar/article/44/D1/D862/2502702/ClinVar-public-archive-of-interpretations-of" target="_blank"> ClinVar: public archive of interpretations of clinically relevant variants</a>. <em>Nucleic Acids Res</em>. 2016 Jan 4;44(D1):D862-8. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/26582918" target="_blank">26582918</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702865/" target="_blank">PMC4702865</a> </p> + +<p> +Azzariti DR, Riggs ER, Niehaus A, Rodriguez LL, Ramos EM, Kattman B, Landrum MJ, Martin CL, Rehm HL. +<a href="https://www.ncbi.nlm.nih.gov/pubmed/29437798" target="_blank"> +Points to consider for sharing variant-level information from clinical genetic testing with +ClinVar</a>. +<em>Cold Spring Harb Mol Case Stud</em>. 2018 Feb;4(1). +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/29437798" target="_blank">29437798</a>; PMC: <a +href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793773/" target="_blank">PMC5793773</a> +</p> +