Tag: Variation

New ClinVar graphical display

Maps clinically significant variants by gene and position!

ClinVar is a freely accessible, public archive of reports of the relationships between human variations and phenotypes, with supporting evidence at NLM/NCBI. To help you access your variants of interest quickly, ClinVar is offering an experimental release of an all-new visualization tool in the search results. This graphical display provides an overview of variants when you search by gene or genomic region (Figures 1 and 2).

Currently the graphical display is implemented as an experiment and will appear for only 10 percent of searches by gene or genomic region, but the links in this post will show the display so you can try it out. Alternatively, if you would like to bring up the graphical display for your gene or genomic region search, you can edit the URL in the address bar to change the default gr=0 to gr=1. For example, the following URL with show the graphical display:

https://www.ncbi.nlm.nih.gov/clinvar/?gr=1&term=DSG2[gene]

Note that you can only get the graphical display with gene or genomic region searches. For other types of searches, you will see the table only.

Gene search display

The display for a gene search highlights small variants within the gene. Large structural variants are also marked as a single dot in the middle of the variation. The interactive display shows the placement of variants on the gene and their clinical significance and allows you to zoom in or pan right / left and limit results to variants in a chosen gene. Figure 1 shows the graphical display as it appears at the top of the search results for the desmoglein 2 (DSG2) gene and how to filter and navigate to variants of interest (Search ClinVar: DSG2[gene]).

Figure 1 (A-D). Graphical display views in ClinVar for variants in DSG2, a gene with many known pathogenic variants.

A. Graphical view showing all variants for the DSG2 gene. Results default to the GRCh37 assembly. You can change to the GRCh38 assembly by clicking the arrow at the upper left (circled in red).

B. You can zoom in by mousing over the 8th exon in the gene diagram, which activates a pop-up menu that allows you to re-display only this region by following the link (red box).

C. Refreshed result for the 8th exon of DSG2 showing a number of variants including pathogenic, benign, and ones with conflicting interpretations of pathogenicity. You can select the filters on the left-hand side of the ClinVar result to limit to variants with characteristics of interest, for example Conflicting Interpretations of pathogenicity.

D. Variants in exon 8 of DSG2 filtered for conflicting interpretations of pathogenicity. You can retrieve individual variants by mousing over the graphic to activate the pop-up menu and following the link (red box).

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Nov 3 Webinar: dbGaP submission improvements and GaPTools

Attention dbGaP submitters! Join us on November 3, 2021 at 12PM US eastern time to learn about data submission and processing improvements to dbGaP, NIH’s database of Genotype and Phenotype, which contains individual-level data associated with human research studies. You will see how we have made submission easier through the Submission Portal using automated preliminary validation and how you can use GaPTools, a stand-alone data validation tool, on your own submission to expedite the submission process. Join us to discover how dbGaP ensures integrity and high-quality in the genomic data that scientists can access to further their research.

- Date: Wed, November 3, 2021
- Time: 12:00 PM – 12:45 PM EDT
- Register

After registering, you will receive a confirmation email with information about attending the webinar. A few days after the live presentation, you can view the recording on the NCBI webinars playlist on the NLM YouTube channel. You can learn about future webinars on the Webinars and Courses page.

Non-human variation data from EVA now available in the Genome Data Viewer

You can now view SNP variation data for many commonly studied animals and plants – including mouse, cow, Drosophila, Arabidopsis, maize, cabbage, and many more – in the Genome Data Viewer (GDV) and other graphical sequence viewers. This data is streamed from the European Variation Archive (EVA) at the European Bioinformatics Institute (EBI).

On any NCBI graphical sequence view you can use the Configure Tracks menu and the Track Configuration Panel to add the track for the EVA RefSNP data. This track is available through the left-hand tab for Remote Variation Data (Figure 1). The EVA RefSNP track displayed on the pig (Sus scrofa) chromosome 12 graphical view is shown in Figure 2.

Config_tracks Figure 1. The Track Configuration panel showing the Remote Variation Data tab and he EVA RefSNP Release 1 track. Select the track checkbox and click Configure to load the track.

pig_snps Figure 2. The graphical sequence viewer showing the region of the growth hormone gene on pig chromosome 12 (NC_010454.4) with the EVA RefSNP Release 1 track at the bottom. The track header has an (R) and a green highlight to indicate that it is remote data streamed from an external website. NCBI is not responsible for the content or availability of these data.

The EVA SNP FTP site has more information about the EVA SNP data release.

Please contact us using the Feedback link on the graphical view to let us know what you think and how we can further improve your experience with the NCBI genome browsers and graphical sequence viewers

dbVar clinical and common structural variants track hub now available

dbVar, NCBI’s database of large-scale genetic variants, has a new track hub for viewing and downloading structural variation (SV) data in popular genome browsers. Initial tracks include Clinical and Common SV datasets. dbVar’s new track hub can be viewed using NCBI’s Genome Data Viewer through the “User Data and Track Hubs” feature (Figure 1) and other genome browsers by selecting “dbVar Hub” from the list of public tracks or by specifying the following URL.

https://ftp.ncbi.nlm.nih.gov/pub/dbVar/sandbox/dbvarhub/hub.txt

Main_Track_Hub_Dial

Figure 1. Loading the dbVar track hub in the Genome Data Viewer. The Track Hubs feature on the left-hand column of the browser allow you to add the track by searching for it or by entering the direct URL. You can select the specific tracks — for example, “NCBI curated common SVs: All populations” — to load from the Configure Track Hubs dialog. Continue reading “dbVar clinical and common structural variants track hub now available” →

April 22 Webinar on NCBI’s ALFA: allele frequency data for variant analysis and interpretation

On Wednesday, April 22, 2020 at 12 PM, join NCBI staff to learn how results from the Allele Frequency Aggregator (ALFA) project will help you interpret the biological impact of common and rare sequence variants. ALFA’s initial release includes analysis of genotype data from ~100K unrestricted dbGaP subjects and provides high-quality allele frequency data now displayed on relevant dbSNP records. In this webinar, you will learn about the data in the recent ALFA release, see how to access the data from the web, FTP, and how to programmatically retrieve data by positions, genes, and other attributes using E-utilities and Variation Services API in Python.

Date and time: Wed, Apr 22, 2020 12:00 PM – 12:45 PM EDT
Register

After registering, you will receive a confirmation email with information about attending the webinar. A few days after the live presentation, you can view the recording on the NCBI YouTube channel. You can learn about future webinars on the Webinars and Courses page.

The ALFA dataset: New aggregated allele frequency from dbGaP and dbSNP now available

NIH’s data sharing policy now allows unrestricted access to genomic summary results for data from NCBI’s Database of Genotypes and Phenotypes (dbGaP). Pooled allele frequency data from dbSNP and the dbGaP summary results are available as the new Allele Frequency Aggregator (ALFA) dataset. The ALFA dataset includes aggregated and harmonized array chip genotyping, exome, and genome sequencing data. The ALFA data are open access and freely available for you to incorporate into your workflows and applications from the dbSNP web pages (Figure 1), through FTP,and the Variation Services API. dbGaP currently has data for more than 2 million study subjects, approximately 1 million of whom have genotype data that is suitable for input into the ALFA dataset. The first release of ALFA contains data on about 100,000 subjects, and we hope to complete processing of data on the other 925,000 subjects within the next year. This volume and variety of data promises unprecedented opportunities to identify genetic factors that influence health and disease. Register to attend our April 22 webinar and read on to learn more.

ALFA Figure 1. ALFA allele frequencies for a variant (rs4988235) in the promotor of the lactase gene showing frequency differences across populations.

Continue reading “The ALFA dataset: New aggregated allele frequency from dbGaP and dbSNP now available” →

New in ClinVar – notifications for changes in the clinical interpretation of variants

We have added a new feature to ClinVar that allows you to follow a particular variant and be notified if the overall clinical interpretation in ClinVar changes, for example from a pathogenic category to a non-pathogenic one. This service will let you know about changes that may require you to update your analysis reports and contact your patients and ordering physicians. The new feature allows you to follow a variant from the variation page (Figure 1). Simply click the “Follow” button to begin receiving notifications.

Follow Figure 1. A ClinVar variant page (VCV000541155.1) showing the ‘Follow’ button. The text on the button changes to ‘Following’ after you add it to your followed variants. Clicking ‘Following’ presents the option to ‘Unfollow’, which removes the variant from the followed list when clicked.

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View BAM alignments in the NCBI genome browsers and sequence viewers sorted by haplotype tag

NCBI’s genome browsers and graphical sequence viewers now allow you to view BAM alignments sorted by haplotype tag. This option is useful for analyzing variants within a sequenced sample and can help you detect or validate structural variants. GDV_bams Figure 1. Remote BAM alignment data sorted by haplotype tag in the Genome Data Viewer. The remote BAM file was added through the “User Data and Track Hubs” feature in GDV. You can load the remote BAM for this example through https://go.usa.gov/xpM9c. The sorted display shows that haplotype 1 contains a significant deletion in this region relative to haplotype 2 and the reference genome assembly. Aligned reads not assigned a haplotype tag in the BAM file are grouped under the heading “haplotype not set” (not shown).

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ClinVar Celebrates 1 Million Submissions

ClinVar is proud to announce the submission of the one millionth record to its database.

The millionth submission was published on Friday, December 20, 2019, a milestone achievement for providing open access to human variant data with asserted consequence to the clinical genetics and research communities.

ClinVar extends its thanks to the many laboratories, partners, and members of the community whose efforts and adoption of the practice of data-sharing paved the way for this achievement. All organizations that contributed to ClinVar’s genetics resources share in this accomplishment, with special recognition reserved for ClinGen and several of their members, including EGL Genetic Diagnostics/Eurofins Clinical Diagnostics, GeneDx, Invitae, and Laboratory for Molecular Medicine/Partners HealthCare Personalized Medicine, whose early submissions helped jump-start ClinVar’s database.

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December 4 Webinar: Human population genetic variation data at NCBI

On Wednesday, December 4, 2019 at 12 PM, NCBI staff will present a webinar on the population variation datasets at NCBI such as 1000 Genomes, ExAC, GnomAD, and TopMed that are currently included on dbSNP records. You will learn how to find the data, and how you can used this information to interpret and prioritize variants for further study. You will also see a preview a new initiative, the dbGaP Allele Frequency Aggregator (ALFA), that is based on more than 150,000 subjects in 60 dbGaP studies.

Date and time: Wed, Dec 4, 2019 12:00 PM – 12:45 PM EDT
Register

Continue reading “December 4 Webinar: Human population genetic variation data at NCBI” →