JSI medical systems GmbH
for research use only
1. Introduction to varSEAK
varSEAK Online offers public
access to the varSEAK database. The varSEAK
database contains variants and
classifications submitted by genetic experts using the
varSEAK Pilot software.
Additionally, information is provided by public databases such as ClinVar, ClinVitae, ExAC, dbSNP, 1000 Genomes Project and the prediction tools and allele frequencies of dbNSFP.
2.1 Searching the database
2.2 Content and Features in the results table
General information about the gene of interest is provided below and to the right of the search field: Below the search field there is the Gene name, Chromosome, Strand, Number of Transcripts, Aliasnames and your selection of up- and downstream ranges. On the right, you can find the Start and End Positions for hg19 and hg38, respectively, and the default transcript the location information is based on.
Only results containing entries in the column varSEAK Classification, ClinVar Classification or ClinVitae Classification will be displayed.
Overhead the results table, the amount of entries for your gene of interest is shown, together with a navigational aid.
Most of the allele frequencies and classifications of the variants from other public databases are directly linked to the respective information about the variant on the respective website. For details, see the description of the respective column.
The results table contains the following information:
|Pos hg19/Pos hg38 (Position)||Lists the chromosomal position of the variant for the respective reference genome.|
|Loc (Location)||Location of the variant. For orientation, location is calculated based on the longest transcript for the gene for all variants in the results table. The name of this default transcript is given on the right of the search field.|
|HGVS||Variant is reported according to HGVS with transcript number (1st line), sequence changes relative to the coding DNA reference sequence (2nd line) and protein reference sequence (3rd line). Click the field to display the complete content if it is abbreviated.|
|varSEAK # of Labs||Count of varSEAK member laboratories that detected this variant.|
|varSEAK Classification||Variant is classified by varSEAK members in five classes (ACMGClassification, e.g. pathogenic (5.0)) (1st line) followed by a detailed explanation of the classification (2nd line), i.e.: it shows how often each classification has been chosen (e.g. 0/0/0/0/2 means that the variant has been classified as pathogenic twice).|
|ClinVar Classification||ClinVar Classification | Clinical significance of variant (ACMG-Classification) from ClinVar.
(http://www.ncbi.nlm.nih.gov/clinvar/, Version: updated weekly)
|ClinVitae Classification||Clinical significance of variant (ACMG-Classification) from ClinVitae. (http://clinvitae.invitae.com/, Version: 2017-10-10)|
|gnomAD AF||Exome Dataset Allele Frequency according to the Genome Aggregation Database (gnomAD). The numbers in the columns are linked to the respective site of the variant in the gnomAD browser. (https://gnomad.broadinstitute.org/, Release r.2.1.0)|
|ExAC AF||Exome allele frequency according to the Aggregation Consortium (ExAc). The numbers in the column are linked to the respective site of the variant in the gnomAD browser with the ExAC dataset selected, as the ExAC browser has been discontinued. However, in contrast to the normal AF shown in varSEAK, this browser shows the adjusted allele frequency (adjAF) (not available for download). (http://exac.broadinstitute.org/, Release r1.0)|
|dbSNP MAF||Global minor allele frequency from the Single Nucleotide Polymorphism database (dbSNP) (usually from 1000 Genomes). (http://www.ncbi.nlm.nih.gov/SNP/ , Build 149)|
|1000 Genomes AF||Allele frequency of variant from 1000 Genomes using allele count (AC) and allele number (AN) values. (http://www.1000genomes.org/ , link is redirected to http://grch37.ensembl.org/index.html , Version: Phase3-v5a)|
|dbNSFP SVM Pred.||Prediction tool to estimate the likelihood that a single-nucleotide
missense variant would damage a protein's structure and function:
tolerated (T) or damaging (D), calculated by the dbNSFP Support
Vector Machine from several prediction tools and conservation
scores. This prediction is only available for coding regions. Splice
regions may have information in some individual prediction tools, but
no overall prediction.
The detailed prediction tool rank scores can be viewed by clicking the (i) button behind the prediction. For each tool, the prediction scores were ranked among all scores of the corresponding tool in dbNSFP. The rankscore is the ratio of the rank of a score over the total number scores of that tool in dbNSFP. If multiple scores exist, only the most damaging rankscore is presented. For some tools the scores were converted first.
dbNSFP also provides Allele Counts and Allele Frequencies from several sources. These are displayed below the prediction tool rank scores (click the (i) button behind the prediction). For a detailed list of the included sources, see the dbNSFP 3.3c readme:
https://drive.google.com/file/d/0B60wROKy6OqcRkNLcG1GSG1OY3M/view (https://sites.google.com/site/jpopgen/dbNSFP , Version: 3.3c)
|Country||Country code of the respective initial submitter's country.|
|Initial Submitter||Laboratory which initially submitted the variant to varSEAK, described with the laboratory name (1st line), and the laboratory address (2nd line). To see the full laboratory name and address hover the cursor over this column to display a tooltip.|