697b862c4a5e14cc41f03dfa5757209898c3d5b8 max Wed May 21 07:14:40 2025 -0700 triangle decorators for the clinvar track, #35750 diff --git src/hg/makeDb/trackDb/human/clinvarAlpha.html src/hg/makeDb/trackDb/human/clinvarAlpha.html new file mode 100644 index 00000000000..6789cd649a2 --- /dev/null +++ src/hg/makeDb/trackDb/human/clinvarAlpha.html @@ -0,0 +1,206 @@ +<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. 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.</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. +</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 on the start position of variants:</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. 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 href="https://github.com/macarthur-lab/clinvar" target="_blank">a converter</a>. +</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, phenotype, 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> +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> +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>In the ClinVar SNV track, protein-truncating mutations are shown with +triangles, inspired by the Decipher transcript browser. The variants with the +following molecular consequences are considered protein-truncating: nonsense, +frameshift variant, splice acceptor variant, splice donor variant. </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> +The variants in the <b>ClinVar Interpretations track</b> are arrange from top to bottom by the variant +classification of each submission: +<ul> + <li><b>P:</b> Pathogenic</li> + <li><b>LP:</b> Likely Pathogenic</li> + <li><b>VUS:</b> Variant of Unknown Significance</li> + <li><b>LB:</b> Likely Benign</li> + <li><b>B:</b> Benign</li> + <li><b>OTH:</b> Others</li> +</ul> +The size of the bead represents +the number of submissions at that genomic position. For better readability, the numbers +are binned into three categories: +<ul> + <li><b>Small-sized beads:</b> 1-2 submissions</li> + <li><b>Medium-sized beads:</b> 3-7 submissions</li> + <li><b>Large-sized beads:</b> 8 or more submissions</li> +</ul> +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/">hg19 README file</a> +on our download site. +</p> + + +<h2>Data updates</h2> +<p>ClinVar publishes a new release on the +<a target="_blank" +href="https://www.ncbi.nlm.nih.gov/feed/rss.cgi?ChanKey=ClinVarNews">first Thursday every month</a>. +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 +<a href="http://hgdownload.soe.ucsc.edu/goldenPath/archive/$db/clinvar/" target="_blank">archive</a> +directory. To display one of these previous versions, paste the URL to one of +the older files into the custom track text input field under "My Data > Custom Tracks".</p> + +<H2>Data access</H2> +<p> +The raw data can be explored interactively with the <a href="../cgi-bin/hgTables">Table Browser</a> +or the <a href="../cgi-bin/hgIntegrator">Data Integrator</a>. The data can be +accessed from scripts through our <a href="https://api.genome.ucsc.edu">API</a>, the track names are +"clinVarMain and "clinVarCnv". + +<p> +For automated download and analysis, the genome annotation is stored in a bigBed file that +can be downloaded from +<a href="http://hgdownload.soe.ucsc.edu/gbdb/$db/bbi/clinvar" 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> + +<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. +If you email them (clinvar@ncbi.nlm.nih.gov), feel free to CC us, it is always good to learn more about ClinVar. +</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> +