rs77469944

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.18475A>G(p.Met6159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,552,142 control chromosomes in the GnomAD database, including 1,108 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M6159I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.042 ( 366 hom., cov: 30)

Exomes 𝑓: 0.012 ( 742 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.41

Publications

11 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 links:

LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)

LUCAT1 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=0.0017308891).

BP6

Variant 5-91150072-A-G is Benign according to our data. Variant chr5-91150072-A-G is described in ClinVar as Benign. ClinVar VariationId is 46298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.18475A>G	p.Met6159Val	missense_variant	Exon 88 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.18475A>G	p.Met6159Val	missense_variant	Exon 88 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

6329

AN:

150442

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00578

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.0800

Gnomad FIN

AF:

0.00158

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.0309

GnomAD2 exomes

AF:

0.0265

AC:

4328

AN:

163388

AF XY:

0.0288

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.00840

Gnomad ASJ exome

AF:

0.00511

Gnomad EAS exome

AF:

0.0447

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00277

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0119

AC:

16652

AN:

1401586

Hom.:

742

Cov.:

AF XY:

0.0138

AC XY:

9526

AN XY:

691652

show subpopulations

African (AFR)

AF:

0.131

AC:

4151

AN:

31630

American (AMR)

AF:

0.0110

AC:

393

AN:

35878

Ashkenazi Jewish (ASJ)

AF:

0.00529

AC:

133

AN:

25130

East Asian (EAS)

AF:

0.0275

AC:

992

AN:

36052

South Asian (SAS)

AF:

0.0862

AC:

6812

AN:

79058

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

49636

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00256

AC:

2766

AN:

1080360

Other (OTH)

AF:

0.0215

AC:

1250

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

662

1325

1987

2650

3312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.0422

AC:

6354

AN:

150556

Hom.:

366

Cov.:

AF XY:

0.0418

AC XY:

3069

AN XY:

73378

show subpopulations

African (AFR)

AF:

0.127

AC:

5176

AN:

40862

American (AMR)

AF:

0.0168

AC:

254

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00578

AC:

AN:

3462

East Asian (EAS)

AF:

0.0443

AC:

227

AN:

5120

South Asian (SAS)

AF:

0.0807

AC:

385

AN:

4768

European-Finnish (FIN)

AF:

0.00158

AC:

AN:

10136

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00251

AC:

170

AN:

67798

Other (OTH)

AF:

0.0306

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

281

563

844

1126

1407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0188

Hom.:

332

Bravo

AF:

0.0469

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.119

AC:

445

ESP6500EA

AF:

0.00208

AC:

ExAC

AF:

0.0213

AC:

2440

Asia WGS

AF:

0.0620

AC:

214

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 02, 2015

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. -

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

- -

Apr 27, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Met6159Val in exon 88 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 11% (347/3046) of African American chromosomes from a broad population by the NHLBI Exome sequencing project (http: //evs.gs.washington.edu/EVS/; dbSNP rs77469944). -

May 15, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.10

T;T;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.72

.;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.98

PhyloP100

3.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.51

.;N;.;.

REVEL

Benign

0.099

Sift

Benign

0.057

.;T;.;.

Sift4G

Uncertain

0.030

.;D;.;.

Polyphen

0.0

B;B;.;.

Vest4

0.21

MPC

0.048

ClinPred

0.014

GERP RS

4.7

Varity_R

0.12

gMVP

0.27

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