rs6889939
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_032119.4(ADGRV1):āc.1652T>Cā(p.Val551Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,613,578 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.015 ( 49 hom., cov: 31)
Exomes š: 0.0017 ( 66 hom. )
Consequence
ADGRV1
NM_032119.4 missense
NM_032119.4 missense
Scores
3
3
6
Clinical Significance
Conservation
PhyloP100: 7.43
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0041161776).
BP6
?
Variant 5-90629352-T-C is Benign according to our data. Variant chr5-90629352-T-C is described in ClinVar as [Benign]. Clinvar id is 46286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90629352-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.1652T>C | p.Val551Ala | missense_variant | 9/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.1652T>C | p.Val551Ala | missense_variant | 9/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000504142.2 | n.418T>C | non_coding_transcript_exon_variant | 3/14 | 5 | ||||
ADGRV1 | ENST00000640109.1 | n.1748T>C | non_coding_transcript_exon_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0154 AC: 2338AN: 151878Hom.: 49 Cov.: 31
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GnomAD3 exomes AF: 0.00398 AC: 992AN: 249040Hom.: 21 AF XY: 0.00292 AC XY: 395AN XY: 135102
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GnomAD4 exome AF: 0.00174 AC: 2543AN: 1461582Hom.: 66 Cov.: 31 AF XY: 0.00148 AC XY: 1077AN XY: 727070
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GnomAD4 genome ? AF: 0.0154 AC: 2339AN: 151996Hom.: 49 Cov.: 31 AF XY: 0.0143 AC XY: 1065AN XY: 74306
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Val551Ala in Exon 09 of GPR98: This variant is not expected to have clinical sig nificance because it has been identified in 5.1% (157/3094) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs6889939). - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 26, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 30, 2018 | - - |
Usher syndrome type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 07, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;D
Vest4
0.63
MVP
0.78
MPC
0.18
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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