rs200946170
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_032119.4(ADGRV1):āc.10563T>Cā(p.Leu3521Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00073 ( 0 hom., cov: 32)
Exomes š: 0.000060 ( 0 hom. )
Consequence
ADGRV1
NM_032119.4 synonymous
NM_032119.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.461
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 5-90745059-T-C is Benign according to our data. Variant chr5-90745059-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197928.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=-0.461 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.10563T>C | p.Leu3521Leu | synonymous_variant | 51/90 | ENST00000405460.9 | NP_115495.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.10563T>C | p.Leu3521Leu | synonymous_variant | 51/90 | 1 | NM_032119.4 | ENSP00000384582.2 |
Frequencies
GnomAD3 genomes AF: 0.000736 AC: 112AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000149 AC: 37AN: 249086Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135118
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461264Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 726912
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GnomAD4 genome AF: 0.000729 AC: 111AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 01, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 03, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 25, 2017 | p.Leu3521Leu in exon 51 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 0.2% (57/24008) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs200946170). - |
ADGRV1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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