Description

This track shows human clinically relevant variants from the ClinVar database, mapped from hg38 to the rheMac10 genome. The mapping uses UCSC's whole-genome alignments and the tool LiftOver. The annotations are somewhat speculative, as LiftOver is not meant to be used for cross-organism mapping. Among others, LiftOver has no notion of phylogenetic trees or protein orthology, so the exact protein to which they are mapped may not be the annotated ortholog. In areas with protein repeats it may have been mapped to the wrong exon. When the genome nucleotide in rheMac10 is different from hg38, the corresponding position could be several basepairs away. Generally, the more different the gene, the harder the mapping. Before planning assays on these data, a manual alignment and annotation of the human and rheMac10 nucleotide or amino acid sequences is recommended.

Display Conventions and Configuration

Genomic locations of ClinVar variants are labeled with the human ClinVar variant descriptions. For example, the label "C>G" usually means that in human, the cDNA nucleotide change is from C>T. On a transcript on the reverse strand, the human genome nucleotide on the forward strand would be G. In rheMac10, the genome may not be G at this position. Zoom in to see the nucleotide in rheMac10, or click the variant to show the human position and nucleotide and the rheMac10 nucleotide.

All ClinVar information related to each is variant is shown on that variant's details page. Hold the mouse over a feature to show the clinical significance of a variant in humans.

Only short variants with a length < 10 bp on the human genome were lifted. A few variants that after lifting result in rheMac10 annotations longer than 30bp were filtered out, too. This can happen in repetitive regions that are hard to align.

Annotations are shaded by clinical annotation: red for pathogenic, dark grey for uncertain significance or not provided and green for benign.

The score of the variants is the number of "stars" in ClinVar. On the track configuration page (above), you can filter the track to show only variants with more than a certain number of stars. For more information on the star rating, see the ClinVar documentation.

Data updates

ClinVar is updated every month, but these mappings are not updated yet on a regular schedule. Please contact us if you are interested in regular updates.

Data access

The raw data can be explored interactively with the Table Browser or the Data Integrator.

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 clinvarLift.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/rheMac10/bbi/clinvarLift.bb -chrom=chr1 -start=0 -end=100000000 stdout

Methods

The hg38 ClinvarMain track was annotated with nucleotides and positions, lifted to rheMac10, filtered again for variants < 30bp and annotated with nucleotides again. The output was converted to the bigBed format. The program that performs the mapping is available on Github.

Credits

Thanks to NCBI for making the ClinVar data available on their FTP site as a tab-separated file.

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