chr5-90693962-G-A

Position:

• chr5-90693962-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.7206G>A	p.Glu2402Glu	synonymous_variant	33/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.7206G>A	p.Glu2402Glu	synonymous_variant	33/90	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

GnomAD3 exomes AF: 0.360 AC: 88481 AN: 246020 Hom.: 17245 AF XY: 0.352 AC XY: 46944 AN XY: 133444

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

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.: 32 AF XY: 0.319 AC XY: 23681 AN XY: 74308

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

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 26, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

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

Other links and lift over

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