rs13157270

Positions:

chr5-90716562-G-A

Variant summary

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

The NM_032119.4(ADGRV1):c.9280G>A(p.Val3094Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 1,613,136 control chromosomes in the GnomAD database, including 5,355 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 0.064 ( 415 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4940 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.23

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=0.0020315647).

BP6

Variant 5-90716562-G-A is Benign according to our data. Variant chr5-90716562-G-A is described in ClinVar as [Benign]. Clinvar id is 46403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90716562-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 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.9280G>A	p.Val3094Ile	missense_variant	43/90	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.9280G>A	p.Val3094Ile	missense_variant	43/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9713

AN:

152058

Hom.:

415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0884

Gnomad OTH

AF:

0.0603

GnomAD3 exomes

AF:

0.0677

AC:

16817

AN:

248542

Hom.:

688

AF XY:

0.0700

AC XY:

9443

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.00285

Gnomad SAS exome

AF:

0.0639

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.0873

Gnomad OTH exome

AF:

0.0742

GnomAD4 exome

AF:

0.0791

AC:

115635

AN:

1460960

Hom.:

4940

Cov.:

AF XY:

0.0790

AC XY:

57426

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.0343

Gnomad4 ASJ exome

AF:

0.0666

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.0633

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0860

Gnomad4 OTH exome

AF:

0.0721

GnomAD4 genome

AF:

0.0639

AC:

9717

AN:

152176

Hom.:

415

Cov.:

AF XY:

0.0631

AC XY:

4695

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.0413

Gnomad4 ASJ

AF:

0.0648

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0641

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.0884

Gnomad4 OTH

AF:

0.0626

Alfa

AF:

0.0791

Hom.:

1071

Bravo

AF:

0.0568

TwinsUK

AF:

0.0866

AC:

321

ALSPAC

AF:

0.0815

AC:

314

ESP6500AA

AF:

0.0286

AC:

106

ESP6500EA

AF:

0.0815

AC:

668

ExAC

AF:

0.0680

AC:

8215

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

EpiCase

AF:

0.0855

EpiControl

AF:

0.0825

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	- -

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	- -

Usher syndrome type 2C

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.084

DANN

Benign

0.87

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.52

.;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.090

.;N

REVEL

Benign

0.0060

Sift

Benign

0.18

.;T

Sift4G

Benign

0.23

.;T

Polyphen

0.010

B;B

Vest4

0.012

MPC

0.042

ClinPred

0.00055

GERP RS

-3.0

Varity_R

0.029

gMVP

0.17

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