rs7729495

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.14905T>C(p.Trp4969Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,612,550 control chromosomes in the GnomAD database, including 1,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 578 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 547 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015814304).

BP6

Variant 5-90807670-T-C is Benign according to our data. Variant chr5-90807670-T-C is described in ClinVar as [Benign]. Clinvar id is 46274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.14905T>C	p.Trp4969Arg	missense_variant	Exon 73 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.14905T>C	p.Trp4969Arg	missense_variant	Exon 73 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7061

AN:

152194

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0122

AC:

3041

AN:

249102

Hom.:

232

AF XY:

0.00937

AC XY:

1267

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.00792

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00493

AC:

7201

AN:

1460238

Hom.:

547

Cov.:

AF XY:

0.00432

AC XY:

3137

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.00868

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000558

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000186

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0466

AC:

7093

AN:

152312

Hom.:

578

Cov.:

AF XY:

0.0447

AC XY:

3331

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00653

Hom.:

138

Bravo

AF:

0.0537

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.168

AC:

619

ESP6500EA

AF:

0.000611

AC:

ExAC

AF:

0.0152

AC:

1833

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000548

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 02, 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. -

May 14, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Trp4969Arg in Exon 73 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 16.6% (495/2990) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs7729495). -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.43

DEOGEN2

Benign

0.071

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.022

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.20

PROVEAN

Benign

2.0

.;N;.

REVEL

Benign

0.098

Sift

Benign

1.0

.;T;.

Sift4G

Benign

0.84

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.053

MutPred

0.41

Gain of disorder (P = 0.0084);Gain of disorder (P = 0.0084);.;

MPC

0.075

ClinPred

0.0036

GERP RS

4.8

Varity_R

0.073

gMVP

0.23

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