NM_032119.4:c.5960C>T

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.5960C>T(p.Pro1987Leu) variant causes a missense change. The variant allele was found at a frequency of 0.345 in 1,612,646 control chromosomes in the GnomAD database, including 98,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8541 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90412 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.87

Publications

42 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=6.9624186E-4).

BP6

Variant 5-90683881-C-T is Benign according to our data. Variant chr5-90683881-C-T is described in ClinVar as Benign. ClinVar VariationId is 46345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.5960C>T	p.Pro1987Leu	missense_variant	Exon 28 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.5960C>T	p.Pro1987Leu	missense_variant	Exon 28 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49749

AN:

151850

Hom.:

8525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.364

AC:

89728

AN:

246604

AF XY:

0.355

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.347

AC:

507360

AN:

1460678

Hom.:

90412

Cov.:

AF XY:

0.345

AC XY:

250508

AN XY:

726526

show subpopulations

African (AFR)

AF:

0.244

AC:

8167

AN:

33472

American (AMR)

AF:

0.571

AC:

25449

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

7180

AN:

26124

East Asian (EAS)

AF:

0.433

AC:

17172

AN:

39662

South Asian (SAS)

AF:

0.328

AC:

28280

AN:

86162

European-Finnish (FIN)

AF:

0.341

AC:

18165

AN:

53338

Middle Eastern (MID)

AF:

0.278

AC:

1601

AN:

5766

European-Non Finnish (NFE)

AF:

0.343

AC:

380817

AN:

1111258

Other (OTH)

AF:

0.340

AC:

20529

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

20560

41119

61679

82238

102798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12382

24764

37146

49528

61910

<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:

0.328

AC:

49779

AN:

151968

Hom.:

8541

Cov.:

AF XY:

0.330

AC XY:

24521

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.255

AC:

10580

AN:

41450

American (AMR)

AF:

0.479

AC:

7310

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

968

AN:

3470

East Asian (EAS)

AF:

0.386

AC:

1994

AN:

5164

South Asian (SAS)

AF:

0.321

AC:

1546

AN:

4816

European-Finnish (FIN)

AF:

0.334

AC:

3523

AN:

10538

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22708

AN:

67950

Other (OTH)

AF:

0.354

AC:

746

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1695

3390

5086

6781

8476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.338

Hom.:

38429

Bravo

AF:

0.341

TwinsUK

AF:

0.332

AC:

1232

ALSPAC

AF:

0.350

AC:

1349

ESP6500AA

AF:

0.251

AC:

934

ESP6500EA

AF:

0.330

AC:

2712

ExAC

AF:

0.352

AC:

42478

Asia WGS

AF:

0.348

AC:

1210

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 23, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 22, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance: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: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. -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C

Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

.;T;T

MetaRNN

Benign

0.00070

T;T;T

MetaSVM

Benign

-0.99

PhyloP100

3.9

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.5

.;D;.

REVEL

Benign

0.23

Sift

Benign

0.15

.;T;.

Sift4G

Uncertain

0.029

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.16

MPC

0.33

ClinPred

0.029

GERP RS

4.8

Varity_R

0.40

gMVP

0.61

Mutation Taster

=91/9

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