rs371831553
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_032119.4(ADGRV1):āc.5221T>Cā(p.Leu1741Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,744 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00079 ( 0 hom., cov: 32)
Exomes š: 0.0016 ( 3 hom. )
Consequence
ADGRV1
NM_032119.4 synonymous
NM_032119.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.325
Genes affected
ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 5-90675353-T-C is Benign according to our data. Variant chr5-90675353-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46333.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=2}. Variant chr5-90675353-T-C is described in Lovd as [Benign]. Variant chr5-90675353-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.325 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.5221T>C | p.Leu1741Leu | synonymous_variant | 24/90 | ENST00000405460.9 | NP_115495.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.5221T>C | p.Leu1741Leu | synonymous_variant | 24/90 | 1 | NM_032119.4 | ENSP00000384582.2 |
Frequencies
GnomAD3 genomes AF: 0.000789 AC: 120AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000835 AC: 208AN: 248996Hom.: 0 AF XY: 0.000881 AC XY: 119AN XY: 135080
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GnomAD4 exome AF: 0.00161 AC: 2356AN: 1461570Hom.: 3 Cov.: 31 AF XY: 0.00152 AC XY: 1105AN XY: 727058
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GnomAD4 genome AF: 0.000789 AC: 120AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74402
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 11, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | ADGRV1: BP4, BP7 - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 07, 2016 | p.Leu1741Leu in Exon 24 of GPR98: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 81/66050 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs371831553). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at