db0c0fec91167570421eaa54d3e88219e35f6c04 gperez2 Wed Jun 25 12:13:05 2025 -0700 Edits to the clinvar description page, refs #35750 diff --git src/hg/makeDb/trackDb/human/clinvarAlpha.html src/hg/makeDb/trackDb/human/clinvarAlpha.html index 6789cd649a2..136847155bb 100644 --- src/hg/makeDb/trackDb/human/clinvarAlpha.html +++ src/hg/makeDb/trackDb/human/clinvarAlpha.html @@ -7,48 +7,48 @@ 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. +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 to 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 +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 @@ -59,134 +59,134 @@ <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 +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 +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 <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 +The variants in the <b>ClinVar Interpretations track</b> are arranged 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 +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 -variant-level, not at case (or patient-specific) level. +the variant-level, not at the 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 +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 +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 <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>. +href="https://www.ncbi.nlm.nih.gov/feed/rss.cgi?ChanKey=ClinVarNews">first Thursday of 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> +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>. +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.