rs950692

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.3141A>G(p.Ala1047Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,534 control chromosomes in the GnomAD database, including 17,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2067 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15096 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.00

Variant links:

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]

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-90647616-A-G is Benign according to our data. Variant chr5-90647616-A-G is described in ClinVar as [Benign]. Clinvar id is 46310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90647616-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.3141A>G	p.Ala1047Ala	synonymous_variant	Exon 17 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.3141A>G	p.Ala1047Ala	synonymous_variant	Exon 17 of 90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1 link	c.444A>G	p.Ala148Ala	synonymous_variant	Exon 7 of 29	5		ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000504142.2 link	n.1907A>G		non_coding_transcript_exon_variant	Exon 11 of 14	5
ADGRV1	ENST00000639676.1 link	n.739A>G		non_coding_transcript_exon_variant	Exon 5 of 11	5

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23922

AN:

152046

Hom.:

2056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.165

AC:

41121

AN:

248978

Hom.:

3957

AF XY:

0.165

AC XY:

22268

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.136

AC:

198756

AN:

1461370

Hom.:

15096

Cov.:

AF XY:

0.138

AC XY:

100544

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.158

AC:

23966

AN:

152164

Hom.:

2067

Cov.:

AF XY:

0.162

AC XY:

12056

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.136

Hom.:

3147

Bravo

AF:

0.158

Asia WGS

AF:

0.300

AC:

1040

AN:

3476

EpiCase

AF:

0.128

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 01, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala1047Ala in exon 17 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction and is listed in dbSNP with an average heterozygous frequency of 33.3% (rs950692). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 05, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Usher syndrome type 2C

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.19

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over