rs2366928

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.10411G>A(p.Glu3471Lys) variant causes a missense change. The variant allele was found at a frequency of 0.711 in 1,605,000 control chromosomes in the GnomAD database, including 409,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45573 hom., cov: 32)

Exomes 𝑓: 0.71 ( 364328 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 4.39

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 -16 ACMG points.

BP6

Variant 5-90728918-G-A is Benign according to our data. Variant chr5-90728918-G-A is described in ClinVar as [Benign]. Clinvar id is 46248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90728918-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 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.10411G>A	p.Glu3471Lys	missense_variant	49/90	ENST00000405460.9	NP_115495.3
LOC105379077	XR_001742802.2 linkuse as main transcript	n.363+11989C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.10411G>A	p.Glu3471Lys	missense_variant	49/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116702

AN:

152048

Hom.:

45497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.902

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.804

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.816

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.750

AC:

185376

AN:

247166

Hom.:

70243

AF XY:

0.745

AC XY:

99855

AN XY:

134072

show subpopulations

Gnomad AFR exome

AF:

0.909

Gnomad AMR exome

AF:

0.852

Gnomad ASJ exome

AF:

0.720

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.728

GnomAD4 exome

AF:

0.705

AC:

1024823

AN:

1452834

Hom.:

364328

Cov.:

AF XY:

0.707

AC XY:

511177

AN XY:

722816

show subpopulations

Gnomad4 AFR exome

AF:

0.908

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.722

Gnomad4 EAS exome

AF:

0.804

Gnomad4 SAS exome

AF:

0.814

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.728

GnomAD4 genome

AF:

0.768

AC:

116841

AN:

152166

Hom.:

45573

Cov.:

AF XY:

0.774

AC XY:

57609

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.903

Gnomad4 AMR

AF:

0.805

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.815

Gnomad4 FIN

AF:

0.733

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.766

Alfa

AF:

0.705

Hom.:

88465

Bravo

AF:

0.779

TwinsUK

AF:

0.676

AC:

2508

ALSPAC

AF:

0.693

AC:

2669

ESP6500AA

AF:

0.904

AC:

3307

ESP6500EA

AF:

0.686

AC:

5602

ExAC

AF:

0.748

AC:

90266

Asia WGS

AF:

0.847

AC:

2943

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.691

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 23, 2010	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Usher syndrome type 2C

Benign:2

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

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.37

.;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

0.86

.;N

REVEL

Benign

0.17

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.084

MPC

0.052

ClinPred

0.0083

GERP RS

5.6

Varity_R

0.055

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: 15

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