rs950692

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.3141A>G(p.Ala1047Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,534 control chromosomes in the GnomAD database, including 17,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2067 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15096 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.00

Publications

20 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BP6

Variant 5-90647616-A-G is Benign according to our data. Variant chr5-90647616-A-G is described in ClinVar as Benign. ClinVar VariationId is 46310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.3141A>G	p.Ala1047Ala	synonymous_variant	Exon 17 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ADGRV1	ENST00000405460.9 link	c.3141A>G	p.Ala1047Ala	synonymous_variant	Exon 17 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1 link	c.444A>G	p.Ala148Ala	synonymous_variant	Exon 7 of 29	5		ENSP00000492531.1
ADGRV1	ENST00000504142.2 link	n.1907A>G		non_coding_transcript_exon_variant	Exon 11 of 14	5
ADGRV1	ENST00000639676.1 link	n.739A>G		non_coding_transcript_exon_variant	Exon 5 of 11	5

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23922

AN:

152046

Hom.:

2056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.165

AC:

41121

AN:

248978

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.136

AC:

198756

AN:

1461370

Hom.:

15096

Cov.:

AF XY:

0.138

AC XY:

100544

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.190

AC:

6367

AN:

33468

American (AMR)

AF:

0.138

AC:

6182

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

5340

AN:

26126

East Asian (EAS)

AF:

0.338

AC:

13393

AN:

39678

South Asian (SAS)

AF:

0.200

AC:

17229

AN:

86238

European-Finnish (FIN)

AF:

0.162

AC:

8673

AN:

53400

Middle Eastern (MID)

AF:

0.169

AC:

977

AN:

5766

European-Non Finnish (NFE)

AF:

0.118

AC:

131110

AN:

1111612

Other (OTH)

AF:

0.157

AC:

9485

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

9362

18725

28087

37450

46812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4970

9940

14910

19880

24850

<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:

0.158

AC:

23966

AN:

152164

Hom.:

2067

Cov.:

AF XY:

0.162

AC XY:

12056

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.184

AC:

7624

AN:

41512

American (AMR)

AF:

0.144

AC:

2193

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

701

AN:

3468

East Asian (EAS)

AF:

0.366

AC:

1889

AN:

5168

South Asian (SAS)

AF:

0.205

AC:

984

AN:

4810

European-Finnish (FIN)

AF:

0.160

AC:

1700

AN:

10598

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8371

AN:

68008

Other (OTH)

AF:

0.173

AC:

365

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

997

1995

2992

3990

4987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.138

Hom.:

6636

Bravo

AF:

0.158

Asia WGS

AF:

0.300

AC:

1040

AN:

3476

EpiCase

AF:

0.128

EpiControl

AF:

0.130

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala1047Ala in exon 17 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction and is listed in dbSNP with an average heterozygous frequency of 33.3% (rs950692). -

Mar 05, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:2

Jan 12, 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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.19

(source)

DANN

Benign

0.48

PhyloP100

-1.0

Mutation Taster

=100/0

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