rs2247870

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/20 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

Publications

58 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 46291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.17626G>A	p.Val5876Ile	missense_variant	Exon 82 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.17626G>A	p.Val5876Ile	missense_variant	Exon 82 of 90	1	NM_032119.4	ENSP00000384582.2		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

GnomAD2 exomes

AF:

0.544

AC:

126932

AN:

233486

AF XY:

0.542

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 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

African (AFR)

AF:

0.184

AC:

5999

AN:

32578

American (AMR)

AF:

0.714

AC:

29167

AN:

40856

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

11958

AN:

25322

East Asian (EAS)

AF:

0.575

AC:

22492

AN:

39144

South Asian (SAS)

AF:

0.534

AC:

43234

AN:

80964

European-Finnish (FIN)

AF:

0.566

AC:

30072

AN:

53130

Middle Eastern (MID)

AF:

0.493

AC:

2803

AN:

5680

European-Non Finnish (NFE)

AF:

0.548

AC:

602344

AN:

1100152

Other (OTH)

AF:

0.522

AC:

31063

AN:

59512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

15785

31570

47355

63140

78925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16990

33980

50970

67960

84950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69786

AN:

152002

Hom.:

18112

Cov.:

AF XY:

0.464

AC XY:

34462

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.198

AC:

8229

AN:

41488

American (AMR)

AF:

0.640

AC:

9752

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1627

AN:

3470

East Asian (EAS)

AF:

0.561

AC:

2891

AN:

5154

South Asian (SAS)

AF:

0.521

AC:

2512

AN:

4820

European-Finnish (FIN)

AF:

0.565

AC:

5969

AN:

10564

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37127

AN:

67950

Other (OTH)

AF:

0.515

AC:

1087

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1735

3470

5205

6940

8675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.520

Hom.:

70864

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

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 02, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is a common benign variant present in roughly half of the general p opulation (dbSNP - rs2247870). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 06, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

3.4

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

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over