rs113938044

Positions:

chr5-90728767-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_032119.4(ADGRV1):c.10260C>T(p.Phe3420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,966 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:7

Conservation

PhyloP100: 0.762

Variant links:

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 links:

LOC105379077 (HGNC:):

LOC105379077 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 5-90728767-C-T is Benign according to our data. Variant chr5-90728767-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46246.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2, Benign=1}. Variant chr5-90728767-C-T is described in Lovd as [Benign]. Variant chr5-90728767-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.762 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.10260C>T	p.Phe3420=	synonymous_variant	49/90	ENST00000405460.9
LOC105379077	XR_001742802.2 linkuse as main transcript	n.363+12140G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.10260C>T	p.Phe3420=	synonymous_variant	49/90	1	NM_032119.4	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00148

AC:

370

AN:

249202

Hom.:

AF XY:

0.00145

AC XY:

196

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00190

AC:

2771

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1334

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00142

AC:

217

AN:

152306

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00201

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00165

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00213

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:5

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	ADGRV1: BP4, BP7 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 04, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	This variant is associated with the following publications: (PMID: 22135276) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 02, 2017	p.Phe3420Phe in exon 49 of GPR98: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, has been identified in 0.3% (27/10150) of Ash kenazi Jewish chromosomes, 0.2% (229/126674) European chromosomes, and 0.2% (57/ 34414) Latino chromosomes by the Genome Aggregation Database (http://gnomad.broa dinstitute.org; dbSNP rs113938044) and is reported as benign in one publication (Le Quesne 2012). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Usher syndrome type 2C

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.1

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over