rs16869039

chr5-90724854-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):c.9771C>T(p.Ser3257=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,612,928 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (126 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (132 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0570

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]

LOC105379077 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 5-90724854-C-T is Benign according to our data. Variant chr5-90724854-C-T is described in ClinVar as [Benign]. Clinvar id is 46408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90724854-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.057 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.9771C>T	p.Ser3257=	synonymous_variant	46/90	ENST00000405460.9
LOC105379077	XR_001742802.2	n.364-9045G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.9771C>T	p.Ser3257=	synonymous_variant	46/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3415 AN: 151952 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00576 AC: 1435 AN: 249014 Hom.: 60 AF XY: 0.00442 AC XY: 597 AN XY: 135092

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00249 AC: 3632 AN: 1460858 Hom.: 132 Cov.: 30 AF XY: 0.00215 AC XY: 1561 AN XY: 726756

Gnomad4 AFR exome AF: 0.0904

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00441

GnomAD4 genome AF: 0.0225 AC: 3427 AN: 152070 Hom.: 126 Cov.: 33 AF XY: 0.0217 AC XY: 1615 AN XY: 74348

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.00413

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0118 Hom.: 28

Bravo AF: 0.0267

Asia WGS AF: 0.00405 AC: 14 AN: 3474

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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	GeneDx	Oct 08, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 16, 2014	Ser3257Ser in exon 46 is not expected to have clinical significance because it d oes not alter an amino acid residue and it has been identified in 9% (249/2924) of African American Chromosomes by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS/ -
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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 26, 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	-0.36
Cadd	Benign	8.6
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs16869039; hg19: chr5-90020671; COSMIC: COSV105343788;