rs10062026

Positions:

Variant summary

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

The NM_032119.4(ADGRV1):c.11599G>A(p.Glu3867Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,529,114 control chromosomes in the GnomAD database, including 94,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3867A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.28 ( 7609 hom., cov: 32)

Exomes 𝑓: 0.35 ( 87371 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.97

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=8.4617734E-4).

BP6

Variant 5-90756472-G-A is Benign according to our data. Variant chr5-90756472-G-A is described in ClinVar as [Benign]. Clinvar id is 46257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90756472-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 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.11599G>A	p.Glu3867Lys	missense_variant	56/90	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.11599G>A	p.Glu3867Lys	missense_variant	56/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43032

AN:

151934

Hom.:

7598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.344

AC:

74321

AN:

216116

Hom.:

14489

AF XY:

0.339

AC XY:

40064

AN XY:

118196

show subpopulations

Gnomad AFR exome

AF:

0.0659

Gnomad AMR exome

AF:

0.568

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.348

AC:

478908

AN:

1377062

Hom.:

87371

Cov.:

AF XY:

0.345

AC XY:

234497

AN XY:

680584

show subpopulations

Gnomad4 AFR exome

AF:

0.0641

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.498

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.283

AC:

43041

AN:

152052

Hom.:

7609

Cov.:

AF XY:

0.287

AC XY:

21314

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0768

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.478

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.332

Hom.:

14291

Bravo

AF:

0.287

TwinsUK

AF:

0.349

AC:

1294

ALSPAC

AF:

0.363

AC:

1400

ESP6500AA

AF:

0.0832

AC:

317

ESP6500EA

AF:

0.331

AC:

2735

ExAC

AF:

0.345

AC:

41720

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 23, 2010	- -

not provided

Benign:2

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: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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.00085

T;T

MetaSVM

Benign

-0.82

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.076

Sift

Benign

0.22

.;T

Sift4G

Benign

0.25

.;T

Polyphen

0.50

P;P

Vest4

0.14

MPC

0.057

ClinPred

0.0091

GERP RS

5.8

Varity_R

0.22

gMVP

0.68

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