dbSNP rs16876822: ADGRV1:p.Glu2402Glu (chr5-90693962-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.7206G>A(p.Glu2402Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,606,424 control chromosomes in the GnomAD database, including 97,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8087 hom., cov: 32)

Exomes 𝑓: 0.35 ( 89238 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.703

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-90693962-G-A is Benign according to our data. Variant chr5-90693962-G-A is described in ClinVar as [Benign]. Clinvar id is 46365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90693962-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.703 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.7206G>A	p.Glu2402Glu	synonymous_variant	Exon 33 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.7206G>A	p.Glu2402Glu	synonymous_variant	Exon 33 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47946

AN:

151910

Hom.:

8074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.360

AC:

88481

AN:

246020

Hom.:

17245

AF XY:

0.352

AC XY:

46944

AN XY:

133444

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.582

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.346

AC:

502513

AN:

1454396

Hom.:

89238

Cov.:

AF XY:

0.343

AC XY:

247735

AN XY:

722126

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.569

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.316

AC:

47965

AN:

152028

Hom.:

8087

Cov.:

AF XY:

0.319

AC XY:

23681

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.329

Hom.:

16750

Bravo

AF:

0.328

Asia WGS

AF:

0.343

AC:

1194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 26, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

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. -

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

Benign:1

Aug 11, 2021

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

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.8

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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