5-90811291-A-G

Position:

chr5-90811291-A-G

Variant summary

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

The ENST00000405460.9(ADGRV1):c.16031A>G(p.Glu5344Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,612,382 control chromosomes in the GnomAD database, including 759,533 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Synonymous variant affecting the same amino acid position (i.e. E5344E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.94 ( 67407 hom., cov: 33)

Exomes 𝑓: 0.97 ( 692126 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.71

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=7.7724985E-7).

BP6

Variant 5-90811291-A-G is Benign according to our data. Variant chr5-90811291-A-G is described in ClinVar as [Benign]. Clinvar id is 46282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90811291-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.16031A>G	p.Glu5344Gly	missense_variant	74/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.16031A>G	p.Glu5344Gly	missense_variant	74/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

142915

AN:

152140

Hom.:

67375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.918

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.993

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.976

Gnomad OTH

AF:

0.936

GnomAD3 exomes

AF:

0.970

AC:

238719

AN:

246210

Hom.:

115886

AF XY:

0.972

AC XY:

129857

AN XY:

133580

show subpopulations

Gnomad AFR exome

AF:

0.846

Gnomad AMR exome

AF:

0.980

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.993

Gnomad FIN exome

AF:

0.981

Gnomad NFE exome

AF:

0.974

Gnomad OTH exome

AF:

0.969

GnomAD4 exome

AF:

0.973

AC:

1421241

AN:

1460124

Hom.:

692126

Cov.:

AF XY:

0.974

AC XY:

707375

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.843

Gnomad4 AMR exome

AF:

0.977

Gnomad4 ASJ exome

AF:

0.923

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.982

Gnomad4 NFE exome

AF:

0.976

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.939

AC:

143001

AN:

152258

Hom.:

67407

Cov.:

AF XY:

0.941

AC XY:

70051

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.962

Gnomad4 ASJ

AF:

0.918

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.993

Gnomad4 FIN

AF:

0.982

Gnomad4 NFE

AF:

0.976

Gnomad4 OTH

AF:

0.937

Alfa

AF:

0.965

Hom.:

114798

Bravo

AF:

0.932

TwinsUK

AF:

0.971

AC:

3599

ALSPAC

AF:

0.975

AC:

3758

ESP6500AA

AF:

0.854

AC:

3209

ESP6500EA

AF:

0.973

AC:

8017

ExAC

AF:

0.968

AC:

116947

Asia WGS

AF:

0.987

AC:

3433

AN:

3478

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 02, 2012	Caucasian frequency = 6466/6644 (ESP data) -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 06, 2013	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.071

T;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.036

.;T;T

MetaRNN

Benign

7.8e-7

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

1.9

.;N;.

REVEL

Benign

0.070

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.065

MPC

0.053

ClinPred

0.0024

GERP RS

4.6

Varity_R

0.060

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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