rs10040165

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.6952-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,584,942 control chromosomes in the GnomAD database, including 94,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8057 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86610 hom. )

Consequence

ADGRV1
NM_032119.4 intron

Scores

Splicing: ADA: 0.0001884

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.469

Publications

15 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-90692595-G-A is Benign according to our data. Variant chr5-90692595-G-A is described in ClinVar as Benign. ClinVar VariationId is 46358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.6952-10G>A		intron_variant	Intron 31 of 89	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.6952-10G>A		intron_variant	Intron 31 of 89	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47886

AN:

151806

Hom.:

8044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.348

AC:

78709

AN:

226266

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.342

AC:

490657

AN:

1433018

Hom.:

86610

Cov.:

AF XY:

0.340

AC XY:

242185

AN XY:

711990

show subpopulations

African (AFR)

AF:

0.202

AC:

6586

AN:

32682

American (AMR)

AF:

0.553

AC:

21803

AN:

39432

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6877

AN:

25576

East Asian (EAS)

AF:

0.432

AC:

16866

AN:

39054

South Asian (SAS)

AF:

0.322

AC:

26224

AN:

81396

European-Finnish (FIN)

AF:

0.340

AC:

17978

AN:

52908

Middle Eastern (MID)

AF:

0.274

AC:

1562

AN:

5710

European-Non Finnish (NFE)

AF:

0.340

AC:

372927

AN:

1096872

Other (OTH)

AF:

0.334

AC:

19834

AN:

59388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

13386

26773

40159

53546

66932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12124

24248

36372

48496

60620

<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:

0.315

AC:

47905

AN:

151924

Hom.:

8057

Cov.:

AF XY:

0.319

AC XY:

23647

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.215

AC:

8926

AN:

41454

American (AMR)

AF:

0.472

AC:

7205

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3466

East Asian (EAS)

AF:

0.387

AC:

1995

AN:

5156

South Asian (SAS)

AF:

0.322

AC:

1547

AN:

4810

European-Finnish (FIN)

AF:

0.334

AC:

3518

AN:

10524

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22629

AN:

67938

Other (OTH)

AF:

0.344

AC:

725

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1668

3335

5003

6670

8338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.335

Hom.:

12058

Bravo

AF:

0.327

Asia WGS

AF:

0.343

AC:

1193

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 19, 2009

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

- -

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

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.030

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