chr5-90653834-A-G

Variant names:

• chr5-90653834-A-G
• rs61740119
• NM_032119.4:c.4260A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.4260A>G​(p.Glu1420Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,612,894 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (46 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.780
• Publications: 5 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 (REVEL=0.014).
• BP6: Variant 5-90653834-A-G is Benign according to our data. Variant chr5-90653834-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00549 (836/152328) while in subpopulation SAS AF = 0.0126 (61/4830). AF 95% confidence interval is 0.0101. There are 3 homozygotes in GnomAd4. There are 408 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.4260A>G	p.Glu1420Glu	synonymous	Exon 20 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.4359A>G		non_coding_transcript_exon	Exon 20 of 90

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.4260A>G	p.Glu1420Glu	synonymous	Exon 20 of 90	ENSP00000384582.2
	ADGRV1	ENST00000640403.1	TSL:5	c.1551A>G	p.Glu517Glu	synonymous	Exon 10 of 29	ENSP00000492531.1
	ADGRV1	ENST00000504142.2	TSL:5	n.3026A>G		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 840 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00562 AC: 1387 AN: 246698 AF XY: 0.00594

Gnomad AFR exome AF: 0.00992

Gnomad AMR exome AF: 0.00728

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00407 AC: 5943 AN: 1460566 Hom.: 46 Cov.: 32 AF XY: 0.00432 AC XY: 3138 AN XY: 726394

African (AFR) AF: 0.00938 AC: 314 AN: 33480

American (AMR) AF: 0.00694 AC: 309 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 307 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0133 AC: 1145 AN: 85894

European-Finnish (FIN) AF: 0.00253 AC: 135 AN: 53354

Middle Eastern (MID) AF: 0.0298 AC: 172 AN: 5768

European-Non Finnish (NFE) AF: 0.00288 AC: 3206 AN: 1111386

Other (OTH) AF: 0.00588 AC: 355 AN: 60346

GnomAD4 genome AF: 0.00549 AC: 836 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74482

African (AFR) AF: 0.00977 AC: 406 AN: 41572

American (AMR) AF: 0.00438 AC: 67 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00472 Hom.: 1

Bravo AF: 0.00564

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADGRV1: BP4, BP7, BS1, BS2

Sep 06, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:3

Aug 28, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Glu1420Glu in exon 20 of GPR98: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence and has been identified in 0.4% (33/8180) of Eu ropean American chromosomes and 1.1% (42/3706) of African American chromosomes f rom a broad population by the NHLBI Exome sequencing project (http://evs.gs.wash ington.edu/EVS/; dbSNP rs61740119).

Apr 30, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Apr 21, 2014

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Usher syndrome type 2C Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.4
DANN	Benign	0.56
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs61740119; hg19: chr5-89949651;