chr5-90704393-C-T

Variant names:

Variant summary

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

The NM_032119.4(ADGRV1):c.8291C>T(p.Ser2764Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,553,964 control chromosomes in the GnomAD database, including 3,387 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 0.053 ( 308 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3079 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

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=0.0017643273).

BP6

Variant 5-90704393-C-T is Benign according to our data. Variant chr5-90704393-C-T is described in ClinVar as [Benign]. Clinvar id is 46387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90704393-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.8291C>T	p.Ser2764Leu	missense_variant	Exon 36 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.8291C>T	p.Ser2764Leu	missense_variant	Exon 36 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0527

AC:

8012

AN:

152016

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0447

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0603

GnomAD3 exomes

AF:

0.0617

AC:

11696

AN:

189596

Hom.:

468

AF XY:

0.0631

AC XY:

6313

AN XY:

100112

show subpopulations

Gnomad AFR exome

AF:

0.00838

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0423

Gnomad EAS exome

AF:

0.0903

Gnomad SAS exome

AF:

0.0813

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0630

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0621

AC:

87032

AN:

1401830

Hom.:

3079

Cov.:

AF XY:

0.0629

AC XY:

43641

AN XY:

693516

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

Gnomad4 AMR exome

AF:

0.0316

Gnomad4 ASJ exome

AF:

0.0398

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.0815

Gnomad4 FIN exome

AF:

0.0958

Gnomad4 NFE exome

AF:

0.0602

Gnomad4 OTH exome

AF:

0.0607

GnomAD4 genome

AF:

0.0527

AC:

8019

AN:

152134

Hom.:

308

Cov.:

AF XY:

0.0549

AC XY:

4079

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.0446

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0936

Gnomad4 FIN

AF:

0.0949

Gnomad4 NFE

AF:

0.0658

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0623

Hom.:

779

Bravo

AF:

0.0455

TwinsUK

AF:

0.0574

AC:

213

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0611

AC:

501

ExAC

AF:

0.0470

AC:

5608

Asia WGS

AF:

0.112

AC:

390

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 16, 2007

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 29, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.62

.;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

.;N;.

REVEL

Benign

0.031

Sift

Benign

0.28

.;T;.

Sift4G

Benign

0.57

.;T;.

Polyphen

0.0030

B;B;.

Vest4

0.042

MPC

0.044

ClinPred

0.0079

GERP RS

3.1

Varity_R

0.12

gMVP

0.38

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