rs56329646

Positions:

chr5-90716495-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_032119.4(ADGRV1):c.9213C>T(p.Asp3071=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,592,634 control chromosomes in the GnomAD database, including 18 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 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 16 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:10

Conservation

PhyloP100: 0.860

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 5-90716495-C-T is Benign according to our data. Variant chr5-90716495-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46402.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=5}. Variant chr5-90716495-C-T is described in Lovd as [Benign]. Variant chr5-90716495-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.86 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00305 (4392/1440442) while in subpopulation MID AF= 0.0178 (101/5676). AF 95% confidence interval is 0.015. There are 16 homozygotes in gnomad4_exome. There are 2219 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.9213C>T	p.Asp3071=	synonymous_variant	43/90	ENST00000405460.9
LOC105379077	XR_001742802.2 linkuse as main transcript	n.364-686G>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.9213C>T	p.Asp3071=	synonymous_variant	43/90	1	NM_032119.4	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

366

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00360

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00255

AC:

620

AN:

242924

Hom.:

AF XY:

0.00290

AC XY:

381

AN XY:

131576

show subpopulations

Gnomad AFR exome

AF:

0.000716

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.000281

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00305

AC:

4392

AN:

1440442

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

2219

AN XY:

714574

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.00169

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00304

Gnomad4 FIN exome

AF:

0.000284

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00372

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152192

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00360

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00248

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:10

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:6

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 01, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ADGRV1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 04, 2015	- -

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 20, 2012	Asp3071Asp in exon 43 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 0.4% (26/6554) of Europe an American chromosomes and 0.01% (3/2960) of African American chromosomes in a broad population by the NHLBI Exome sequencing project (http://evs.gs.washington .edu/EVS/; dbSNP rs56329646). -

Usher syndrome type 2C

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.31

CADD

Benign

8.3

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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