5-90823476-C-T

Position:

• chr5-90823476-C-T

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.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 (★★).

• 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

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=-0.77).
• BP6: Variant 5-90823476-C-T is Benign according to our data. Variant chr5-90823476-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.16248C>T	p.Val5416Val	synonymous_variant	76/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.16248C>T	p.Val5416Val	synonymous_variant	76/90	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

GnomAD3 exomes AF: 0.0500 AC: 12461 AN: 249090 Hom.: 970 AF XY: 0.0523 AC XY: 7064 AN XY: 135122

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 SAS exome AF: 0.115

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

Gnomad4 AFR exome AF: 0.00355

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0468

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.0394

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

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0155 Hom.: 59

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 16, 2010	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2013	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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 11, 2017	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.12
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

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