5-90683874-A-G

Position:

chr5-90683874-A-G

Variant summary

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

The NM_032119.4(ADGRV1):c.5953A>G(p.Asn1985Asp) variant causes a missense change. The variant allele was found at a frequency of 0.148 in 1,612,926 control chromosomes in the GnomAD database, including 21,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3734 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17443 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.02

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=0.004298836).

BP6

Variant 5-90683874-A-G is Benign according to our data. Variant chr5-90683874-A-G is described in ClinVar as [Benign]. Clinvar id is 46344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90683874-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.5953A>G	p.Asn1985Asp	missense_variant	28/90	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.5953A>G	p.Asn1985Asp	missense_variant	28/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30455

AN:

151934

Hom.:

3717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.180

AC:

44514

AN:

246954

Hom.:

4917

AF XY:

0.177

AC XY:

23694

AN XY:

133932

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.142

AC:

207758

AN:

1460874

Hom.:

17443

Cov.:

AF XY:

0.144

AC XY:

104475

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.201

AC:

30504

AN:

152052

Hom.:

3734

Cov.:

AF XY:

0.204

AC XY:

15153

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.129

Hom.:

1149

Bravo

AF:

0.208

TwinsUK

AF:

0.116

AC:

430

ALSPAC

AF:

0.127

AC:

490

ESP6500AA

AF:

0.316

AC:

1176

ESP6500EA

AF:

0.132

AC:

1082

ExAC

AF:

0.182

AC:

22007

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 25, 2014	- -
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. -
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	Feb 01, 2011	Asn1985Asp in exon 28 of GPR98: This variant is not expected to have clinical si gnificance because it is listed in dbSNP with a heterozygous frequency of 10-34% (rs41303352). -

Usher syndrome type 2C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
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

Benign

0.22

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

.;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.54

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.067

Sift

Benign

0.19

.;T;.

Sift4G

Benign

0.20

.;T;.

Polyphen

0.0030

B;B;.

Vest4

0.055

MPC

0.33

ClinPred

0.027

GERP RS

4.5

Varity_R

0.25

gMVP

0.45

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