rs2438378

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.16279G>A(p.Val5427Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,940 control chromosomes in the GnomAD database, including 798,880 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 0.97 ( 72243 hom., cov: 32)

Exomes 𝑓: 1.0 ( 726637 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.120

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:

ADGRV1 (HGNC:):

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=6.644323E-7).

BP6

Variant 5-90823507-G-A is Benign according to our data. Variant chr5-90823507-G-A is described in ClinVar as [Benign]. Clinvar id is 46285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90823507-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.16279G>A	p.Val5427Met	missense_variant	76/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.16279G>A	p.Val5427Met	missense_variant	76/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

148114

AN:

152156

Hom.:

72197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.970

GnomAD3 exomes

AF:

0.993

AC:

247487

AN:

249218

Hom.:

122946

AF XY:

0.995

AC XY:

134512

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.997

AC:

1457301

AN:

1461666

Hom.:

726637

Cov.:

AF XY:

0.997

AC XY:

725234

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.906

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.993

GnomAD4 genome

AF:

0.973

AC:

148217

AN:

152274

Hom.:

72243

Cov.:

AF XY:

0.974

AC XY:

72526

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.911

Gnomad4 AMR

AF:

0.986

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.970

Alfa

AF:

0.995

Hom.:

130642

Bravo

AF:

0.970

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

0.999

AC:

3852

ESP6500AA

AF:

0.914

AC:

3541

ESP6500EA

AF:

0.999

AC:

8270

ExAC

AF:

0.992

AC:

119849

Asia WGS

AF:

0.997

AC:

3466

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 10, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 15, 2014	- -
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:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.083

DANN

Benign

0.55

DEOGEN2

Benign

0.067

T;T;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.071

.;T;T

MetaRNN

Benign

6.6e-7

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.21

PROVEAN

Benign

0.33

.;N;.

REVEL

Benign

0.093

Sift

Benign

0.30

.;T;.

Sift4G

Benign

0.26

.;T;.

Polyphen

0.0010

B;B;.

Vest4

0.056

MPC

0.048

ClinPred

0.015

GERP RS

-9.7

Varity_R

0.020

gMVP

0.31

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