5-90823476-C-T

Variant names:

• chr5-90823476-C-T
• rs3763073
• NM_032119.4:c.16248C>T

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.16248C>T​(p.Val5416Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,782 control chromosomes in the GnomAD database, including 2,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V5416V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.027 (280 hom., cov: 32)
  • Exomes 𝑓: 0.028 (2632 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.723
• Publications: 16 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=-0.77).
• BP6: Variant 5-90823476-C-T is Benign according to our data. Variant chr5-90823476-C-T is described in ClinVar as Benign. ClinVar VariationId is 46284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.723 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.16248C>T	p.Val5416Val	synonymous_variant	Exon 76 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.16248C>T	p.Val5416Val	synonymous_variant	Exon 76 of 90	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4158 AN: 152132 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0500 AC: 12461 AN: 249090 AF XY: 0.0523

Gnomad AFR exome AF: 0.00349

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0279 AC: 40754 AN: 1461532 Hom.: 2632 Cov.: 30 AF XY: 0.0306 AC XY: 22270 AN XY: 727030

African (AFR) AF: 0.00355 AC: 119 AN: 33476

American (AMR) AF: 0.0181 AC: 810 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 549 AN: 26130

East Asian (EAS) AF: 0.291 AC: 11547 AN: 39672

South Asian (SAS) AF: 0.115 AC: 9931 AN: 86200

European-Finnish (FIN) AF: 0.0468 AC: 2500 AN: 53402

Middle Eastern (MID) AF: 0.0337 AC: 194 AN: 5764

European-Non Finnish (NFE) AF: 0.0114 AC: 12728 AN: 1111802

Other (OTH) AF: 0.0394 AC: 2376 AN: 60368

GnomAD4 genome AF: 0.0273 AC: 4149 AN: 152250 Hom.: 280 Cov.: 32 AF XY: 0.0313 AC XY: 2328 AN XY: 74450

African (AFR) AF: 0.00347 AC: 144 AN: 41554

American (AMR) AF: 0.0241 AC: 368 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1439 AN: 5168

South Asian (SAS) AF: 0.129 AC: 620 AN: 4822

European-Finnish (FIN) AF: 0.0412 AC: 437 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 1001 AN: 68028

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0190 Hom.: 343

Bravo AF: 0.0237

Asia WGS AF: 0.174 AC: 604 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0130

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 16, 2010

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

- -

Feb 27, 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. -

not provided Benign:2

Dec 11, 2017

Athena Diagnostics

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 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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: rs3763073; hg19: chr5-90119293; COSMIC: COSV67980983;