rs141701016
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_032119.4(ADGRV1):c.12527+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,613,048 control chromosomes in the GnomAD database, including 2 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: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
ADGRV1
NM_032119.4 splice_donor_region, intron
NM_032119.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001513
2
Clinical Significance
Conservation
PhyloP100: -0.0250
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 -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 5-90776582-G-T is Benign according to our data. Variant chr5-90776582-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178367.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=5, Benign=1}. Variant chr5-90776582-G-T is described in Lovd as [Benign]. Variant chr5-90776582-G-T is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.12527+6G>T | splice_donor_region_variant, intron_variant | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.12527+6G>T | splice_donor_region_variant, intron_variant | 1 | NM_032119.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00176 AC: 268AN: 152034Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000450 AC: 112AN: 248946Hom.: 0 AF XY: 0.000392 AC XY: 53AN XY: 135062
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GnomAD4 exome AF: 0.000194 AC: 284AN: 1460898Hom.: 1 Cov.: 31 AF XY: 0.000197 AC XY: 143AN XY: 726752
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GnomAD4 genome ? AF: 0.00178 AC: 271AN: 152150Hom.: 1 Cov.: 32 AF XY: 0.00179 AC XY: 133AN XY: 74370
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:9
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 14, 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 | Invitae | Jan 30, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2019 | - - |
not specified Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 06, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 12527+6G>T in Intron 61 of GPR98: This variant is not expected to have clinical significance because it has been identified in 0.6% (17/3032) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs141701016). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 16, 2016 | - - |
Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 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. - |
ADGRV1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at