rs61744480

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_032119.4(ADGRV1):c.1522A>C(p.Ile508Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00217 in 1,572,574 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 3 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:7

Conservation

PhyloP100: 6.89

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 -9 ACMG points.

BP6

Variant 5-90629222-A-C is Benign according to our data. Variant chr5-90629222-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 163563.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Benign=1, Uncertain_significance=3}. Variant chr5-90629222-A-C is described in Lovd as [Benign]. Variant chr5-90629222-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00221 (3134/1420384) while in subpopulation MID AF= 0.00593 (33/5564). AF 95% confidence interval is 0.00434. There are 3 homozygotes in gnomad4_exome. There are 1604 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.1522A>C	p.Ile508Leu	missense_variant	Exon 9 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.1522A>C	p.Ile508Leu	missense_variant	Exon 9 of 90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000504142.2 link	n.288A>C		non_coding_transcript_exon_variant	Exon 3 of 14	5
ADGRV1	ENST00000640109.1 link	n.1618A>C		non_coding_transcript_exon_variant	Exon 9 of 9	5
ADGRV1	ENST00000640083.1 link	n.*150A>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00274

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00214

AC:

484

AN:

226402

Hom.:

AF XY:

0.00225

AC XY:

276

AN XY:

122778

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00262

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.00252

Gnomad NFE exome

AF:

0.00269

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00221

AC:

3134

AN:

1420384

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

1604

AN XY:

702550

show subpopulations

Gnomad4 AFR exome

AF:

0.000407

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00315

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.00375

Gnomad4 NFE exome

AF:

0.00222

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152190

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00274

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00172

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000274

AC:

ESP6500EA

AF:

0.00294

AC:

ExAC

AF:

0.00212

AC:

256

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 17, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30180840, 26969326) -

Dec 29, 2018

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADGRV1: BS2 -

not specified

Benign:3

Feb 03, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile508Leu in Exon 09 of GPR98: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (24/6556) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs61744480). -

Apr 09, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2C

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Retinal dystrophy

Uncertain:1

Jan 01, 2023

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ADGRV1-related disorder

Benign:1

Sep 17, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

.;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.82

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.21

Sift

Benign

0.097

.;T

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;D

Vest4

0.82

MVP

0.65

MPC

0.066

ClinPred

0.040

GERP RS

3.1

Varity_R

0.24

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 6

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