rs73181648

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.3956G>A(p.Arg1319Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,613,868 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1319W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 4 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.64

Publications

4 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=0.008273959).

BP6

Variant 5-90653530-G-A is Benign according to our data. Variant chr5-90653530-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00349 (531/152234) while in subpopulation AFR AF = 0.0125 (519/41536). AF 95% confidence interval is 0.0116. There are 4 homozygotes in GnomAd4. There are 255 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.3956G>A	p.Arg1319Gln	missense_variant	Exon 20 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.3956G>A	p.Arg1319Gln	missense_variant	Exon 20 of 90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1 link	c.1247G>A	p.Arg416Gln	missense_variant	Exon 10 of 29	5		ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000504142.2 link	n.2722G>A		non_coding_transcript_exon_variant	Exon 14 of 14	5
ADGRV1	ENST00000639676.1 link	n.1554G>A		non_coding_transcript_exon_variant	Exon 8 of 11	5

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000840

AC:

209

AN:

248940

AF XY:

0.000607

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000309

AC:

451

AN:

1461634

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

189

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.0116

AC:

387

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111852

Other (OTH)

AF:

0.000596

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152234

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

255

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0125

AC:

519

AN:

41536

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00390

ESP6500AA

AF:

0.0110

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00105

AC:

127

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jul 15, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 17, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30180840) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 06, 2020

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg1319Gln in Exon 20 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 1.1% (36/3232) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs73181648). -

Apr 03, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D;D

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

7.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.1

.;N;.

REVEL

Benign

0.21

Sift

Benign

0.092

.;T;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.56

MVP

0.67

MPC

0.20

ClinPred

0.033

GERP RS

5.4

Varity_R

0.24

gMVP

0.80

Mutation Taster

=77/23

polymorphism

(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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rs73181648

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