rs74632023

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.13037C>T(p.Pro4346Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00127 in 1,612,880 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 14 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.42

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=0.0114275515).

BP6

Variant 5-90779052-C-T is Benign according to our data. Variant chr5-90779052-C-T is described in ClinVar as [Benign]. Clinvar id is 46265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90779052-C-T is described in Lovd as [Likely_benign]. Variant chr5-90779052-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00659 (1003/152086) while in subpopulation AFR AF= 0.0234 (969/41480). AF 95% confidence interval is 0.0221. There are 15 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.13037C>T	p.Pro4346Leu	missense_variant	Exon 64 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.13037C>T	p.Pro4346Leu	missense_variant	Exon 64 of 90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000425867.3 link	c.1991C>T	p.Pro664Leu	missense_variant	Exon 12 of 38	5		ENSP00000392618.3	A0A1X7SBU6
ADGRV1	ENST00000640464.1 link	n.3456C>T		non_coding_transcript_exon_variant	Exon 21 of 21	5
ADGRV1	ENST00000639431.1 link	n.265+102843C>T		intron_variant	Intron 2 of 4	5		ENSP00000491057.1	A0A1W2PNS5

Frequencies

GnomAD3 genomes

AF:

0.00657

AC:

998

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00191

AC:

474

AN:

248416

Hom.:

AF XY:

0.00150

AC XY:

202

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000719

AC:

1050

AN:

1460794

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00659

AC:

1003

AN:

152086

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

474

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00750

ESP6500AA

AF:

0.0220

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00239

AC:

289

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro4346Leu in Exon 64 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 2.5% (76/3026) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs74632023). -

Aug 13, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C

Benign:1

Jan 03, 2022

Fulgent Genetics, Fulgent Genetics

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

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.82

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-6.2

.;D;.

REVEL

Benign

0.25

Sift

Uncertain

0.0090

.;D;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.75

MVP

0.71

MPC

0.32

ClinPred

0.034

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.39

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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