rs2247870

Positions:

chr5-90855772-G-A

Variant summary

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

The NM_032119.4(ADGRV1):c.17626G>A(p.Val5876Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,589,340 control chromosomes in the GnomAD database, including 232,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18112 hom., cov: 32)

Exomes 𝑓: 0.54 ( 214827 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.35

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=2.5032716E-6).

BP6

Variant 5-90855772-G-A is Benign according to our data. Variant chr5-90855772-G-A is described in ClinVar as [Benign]. Clinvar id is 46291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90855772-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 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.17626G>A	p.Val5876Ile	missense_variant	82/90	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.17626G>A	p.Val5876Ile	missense_variant	82/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69763

AN:

151882

Hom.:

18098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.510

GnomAD3 exomes

AF:

0.544

AC:

126932

AN:

233486

Hom.:

36252

AF XY:

0.542

AC XY:

68509

AN XY:

126358

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.727

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.539

Gnomad SAS exome

AF:

0.534

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.542

AC:

779132

AN:

1437338

Hom.:

214827

Cov.:

AF XY:

0.541

AC XY:

385841

AN XY:

713248

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.714

Gnomad4 ASJ exome

AF:

0.472

Gnomad4 EAS exome

AF:

0.575

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.459

AC:

69786

AN:

152002

Hom.:

18112

Cov.:

AF XY:

0.464

AC XY:

34462

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.640

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.521

Gnomad4 FIN

AF:

0.565

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.528

Hom.:

49191

Bravo

AF:

0.451

TwinsUK

AF:

0.538

AC:

1996

ALSPAC

AF:

0.550

AC:

2121

ESP6500AA

AF:

0.195

AC:

759

ESP6500EA

AF:

0.547

AC:

4531

ExAC

AF:

0.536

AC:

64763

Asia WGS

AF:

0.563

AC:

1958

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 06, 2018	- -
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	Sep 02, 2010	This variant is a common benign variant present in roughly half of the general p opulation (dbSNP - rs2247870). -

Usher syndrome type 2C

Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

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	This variant is associated with the following publications: (PMID: 28991256) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.19

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.50

.;T;T

MetaRNN

Benign

0.0000025

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.26

P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.43

.;N;.

REVEL

Benign

0.094

Sift

Benign

0.24

.;T;.

Sift4G

Benign

0.19

.;T;.

Polyphen

0.58

P;P;.

Vest4

0.12

MPC

0.042

ClinPred

0.0084

GERP RS

4.6

Varity_R

0.039

gMVP

0.20

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