rs16876822

Variant names:

• chr5-90693962-G-A
• rs16876822
• NM_032119.4:c.7206G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90693962-G-A
• chr5-90693962-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.703
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 46365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.7206G>A	p.Glu2402Glu	synonymous_variant	Exon 33 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.7206G>A	p.Glu2402Glu	synonymous_variant	Exon 33 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47946 AN: 151910 Hom.: 8074 Cov.: 32

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

GnomAD2 exomes AF: 0.360 AC: 88481 AN: 246020 AF XY: 0.352

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 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.: 37 AF XY: 0.343 AC XY: 247735 AN XY: 722126

African (AFR) AF: 0.205 AC: 6833 AN: 33352

American (AMR) AF: 0.569 AC: 25215 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7073 AN: 25974

East Asian (EAS) AF: 0.433 AC: 17095 AN: 39482

South Asian (SAS) AF: 0.328 AC: 28181 AN: 85932

European-Finnish (FIN) AF: 0.341 AC: 18130 AN: 53226

Middle Eastern (MID) AF: 0.274 AC: 1572 AN: 5734

European-Non Finnish (NFE) AF: 0.342 AC: 378218 AN: 1106374

Other (OTH) AF: 0.337 AC: 20196 AN: 59996

GnomAD4 genome AF: 0.316 AC: 47965 AN: 152028 Hom.: 8087 Cov.: 32 AF XY: 0.319 AC XY: 23681 AN XY: 74308

African (AFR) AF: 0.215 AC: 8931 AN: 41470

American (AMR) AF: 0.474 AC: 7233 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.386 AC: 1990 AN: 5158

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10562

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22647 AN: 67968

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.328 Hom.: 26261

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

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
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16876822; hg19: chr5-89989779; COSMIC: COSV67980898; COSMIC: COSV67980898;