rs41304884

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032119.4(ADGRV1):c.16164A>G(p.Arg5388Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,566,476 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 17 hom., cov: 32)

Exomes 𝑓: 0.017 ( 312 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.885

Publications

5 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 (BayesDel_noAF=-0.84).

BP6

Variant 5-90815704-A-G is Benign according to our data. Variant chr5-90815704-A-G is described in ClinVar as Benign. ClinVar VariationId is 46283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.885 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0137 (2087/152280) while in subpopulation SAS AF = 0.0483 (233/4826). AF 95% confidence interval is 0.0432. There are 17 homozygotes in GnomAd4. There are 1043 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.16164A>G	p.Arg5388Arg	synonymous_variant	Exon 75 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.16164A>G	p.Arg5388Arg	synonymous_variant	Exon 75 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2092

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0484

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.0171

AC:

3139

AN:

184080

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.00873

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00867

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00888

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0172

AC:

24315

AN:

1414196

Hom.:

312

Cov.:

AF XY:

0.0182

AC XY:

12725

AN XY:

699588

show subpopulations

African (AFR)

AF:

0.00857

AC:

278

AN:

32444

American (AMR)

AF:

0.0109

AC:

415

AN:

38086

Ashkenazi Jewish (ASJ)

AF:

0.00765

AC:

194

AN:

25348

East Asian (EAS)

AF:

0.0000796

AC:

AN:

37710

South Asian (SAS)

AF:

0.0462

AC:

3702

AN:

80166

European-Finnish (FIN)

AF:

0.00836

AC:

426

AN:

50986

Middle Eastern (MID)

AF:

0.0477

AC:

272

AN:

5708

European-Non Finnish (NFE)

AF:

0.0166

AC:

17972

AN:

1084908

Other (OTH)

AF:

0.0179

AC:

1053

AN:

58840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

1030

2060

3090

4120

5150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.0137

AC:

2087

AN:

152280

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00864

AC:

359

AN:

41560

American (AMR)

AF:

0.0126

AC:

192

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0483

AC:

233

AN:

4826

European-Finnish (FIN)

AF:

0.00923

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0166

AC:

1128

AN:

68022

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

197

295

394

492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0152

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 27, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 10, 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. -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg5388Arg in exon 75 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 0.2% (13/6503) of Europe an American chromosomes and 0.8% (27/3116) of African American chromosomes from a broad population by the NHLBI Exome sequencing project (http://evs.gs.washingt on.edu/EVS/; dbSNP rs41304884), and is reported as benign (Le Quesne Stabel 201 2). -

Usher syndrome type 2C

Benign:1

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: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

0.65

(source)

DANN

Benign

0.38

PhyloP100

-0.89

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