rs16868972

Positions:

chr5-90683933-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000405460.9(ADGRV1):c.6012G>T(p.Leu2004Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,170 control chromosomes in the GnomAD database, including 27,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5520 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21533 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043822527).

BP6

Variant 5-90683933-G-T is Benign according to our data. Variant chr5-90683933-G-T is described in ClinVar as [Benign]. Clinvar id is 46346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90683933-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.6012G>T	p.Leu2004Phe	missense_variant	28/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.6012G>T	p.Leu2004Phe	missense_variant	28/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36050

AN:

151864

Hom.:

5498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.198

AC:

49141

AN:

247808

Hom.:

6035

AF XY:

0.194

AC XY:

26021

AN XY:

134402

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.409

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.157

AC:

228788

AN:

1461188

Hom.:

21533

Cov.:

AF XY:

0.158

AC XY:

114721

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.238

AC:

36110

AN:

151982

Hom.:

5520

Cov.:

AF XY:

0.240

AC XY:

17796

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.426

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.165

Hom.:

5011

Bravo

AF:

0.250

TwinsUK

AF:

0.126

AC:

466

ALSPAC

AF:

0.138

AC:

533

ESP6500AA

AF:

0.418

AC:

1557

ESP6500EA

AF:

0.144

AC:

1183

ExAC

AF:

0.203

AC:

24458

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 01, 2011	Leu2004Phe in exon 28 of GPR98: This variant is not expected to have clinical si gnificance because it is listed in dbSNP with an average heterozygous frequency of 42.7% (rs16868972). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 25, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Usher syndrome type 2C

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.87

.;D;D

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.26

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

.;N;.

REVEL

Benign

0.19

Sift

Benign

0.043

.;D;.

Sift4G

Uncertain

0.048

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.084

MutPred

0.56

Gain of methylation at K2005 (P = 0.0283);Gain of methylation at K2005 (P = 0.0283);.;

MPC

0.33

ClinPred

0.035

GERP RS

3.5

Varity_R

0.27

gMVP

0.38

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

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