rs16869032

Positions:

Variant summary

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

The NM_032119.4(ADGRV1):c.9743G>A(p.Gly3248Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,608,614 control chromosomes in the GnomAD database, including 17,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1968 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15453 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 7.96

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:

LOC105379077 (HGNC:):

LOC105379077 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=0.0027834475).

BP6

Variant 5-90721054-G-A is Benign according to our data. Variant chr5-90721054-G-A is described in ClinVar as [Benign]. Clinvar id is 46407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90721054-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.9743G>A	p.Gly3248Asp	missense_variant	45/90	ENST00000405460.9	NP_115495.3
LOC105379077	XR_001742802.2 linkuse as main transcript	n.364-5245C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.9743G>A	p.Gly3248Asp	missense_variant	45/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22996

AN:

151816

Hom.:

1955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.166

AC:

41104

AN:

247700

Hom.:

4181

AF XY:

0.166

AC XY:

22276

AN XY:

134352

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.136

AC:

198326

AN:

1456680

Hom.:

15453

Cov.:

AF XY:

0.138

AC XY:

100235

AN XY:

724662

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.371

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.152

AC:

23035

AN:

151934

Hom.:

1968

Cov.:

AF XY:

0.156

AC XY:

11621

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.136

Hom.:

2585

Bravo

AF:

0.150

TwinsUK

AF:

0.115

AC:

426

ALSPAC

AF:

0.127

AC:

488

ESP6500AA

AF:

0.154

AC:

584

ESP6500EA

AF:

0.131

AC:

1081

ExAC

AF:

0.166

AC:

20042

Asia WGS

AF:

0.327

AC:

1134

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 01, 2011	Gly3248Asp in exon 45 of GPR98: This variant is not expected to have clinical si gnificance because it is listed in dbSNP with a heterozygous frequency of 16-56% (rs16869032) -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2013	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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Usher syndrome type 2C

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.79

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

3.2e-7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.22

Sift

Uncertain

0.010

.;D

Sift4G

Uncertain

0.0040

.;D

Polyphen

0.99

D;D

Vest4

0.32

MPC

0.34

ClinPred

0.033

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.76

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