rs41311343

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.10577T>C(p.Met3526Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,534 control chromosomes in the GnomAD database, including 845 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 63 hom., cov: 32)

Exomes 𝑓: 0.030 ( 782 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -2.04

Publications

13 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=0.0023483634).

BP6

Variant 5-90745073-T-C is Benign according to our data. Variant chr5-90745073-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0227 (3451/152292) while in subpopulation NFE AF = 0.0352 (2395/68002). AF 95% confidence interval is 0.034. There are 63 homozygotes in GnomAd4. There are 1656 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 63 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.10577T>C	p.Met3526Thr	missense_variant	Exon 51 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.10577T>C	p.Met3526Thr	missense_variant	Exon 51 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3451

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0352

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0231

AC:

5748

AN:

249126

AF XY:

0.0232

show subpopulations

Gnomad AFR exome

AF:

0.00484

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.00295

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0299

AC:

43629

AN:

1461242

Hom.:

782

Cov.:

AF XY:

0.0294

AC XY:

21344

AN XY:

726924

show subpopulations

African (AFR)

AF:

0.00475

AC:

159

AN:

33476

American (AMR)

AF:

0.0114

AC:

510

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

321

AN:

26130

East Asian (EAS)

AF:

0.00224

AC:

AN:

39668

South Asian (SAS)

AF:

0.0157

AC:

1356

AN:

86244

European-Finnish (FIN)

AF:

0.0359

AC:

1914

AN:

53388

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0340

AC:

37810

AN:

1111484

Other (OTH)

AF:

0.0239

AC:

1442

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1966

3932

5897

7863

9829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1350

2700

4050

5400

6750

<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:

0.0227

AC:

3451

AN:

152292

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1656

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00577

AC:

240

AN:

41582

American (AMR)

AF:

0.0142

AC:

217

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.00347

AC:

AN:

5180

South Asian (SAS)

AF:

0.0145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0338

AC:

359

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0352

AC:

2395

AN:

68002

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0278

Hom.:

145

Bravo

AF:

0.0197

TwinsUK

AF:

0.0305

AC:

113

ALSPAC

AF:

0.0376

AC:

145

ESP6500AA

AF:

0.00476

AC:

ESP6500EA

AF:

0.0304

AC:

250

ExAC

AF:

0.0232

AC:

2799

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0297

EpiControl

AF:

0.0277

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Apr 10, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

May 14, 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. -

Nov 07, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jan 26, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 12, 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

0.061

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.046

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.063

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.25

.;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

PhyloP100

-2.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.090

.;N

REVEL

Benign

0.045

Sift

Benign

0.57

.;T

Sift4G

Benign

0.57

.;T

Polyphen

0.0050

B;B

Vest4

0.028

MPC

0.053

ClinPred

0.0018

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.048

gMVP

0.30

Mutation Taster

=73/27

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