rs17554631

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.13599A>G(p.Thr4533Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,610,940 control chromosomes in the GnomAD database, including 34,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2448 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32520 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.430

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 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-90784003-A-G is Benign according to our data. Variant chr5-90784003-A-G is described in ClinVar as Benign. ClinVar VariationId is 46268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.13599A>G	p.Thr4533Thr	synonymous_variant	Exon 67 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.13599A>G	p.Thr4533Thr	synonymous_variant	Exon 67 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23447

AN:

152000

Hom.:

2447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.162

AC:

40096

AN:

246750

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.0963

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.201

AC:

293874

AN:

1458822

Hom.:

32520

Cov.:

AF XY:

0.199

AC XY:

144460

AN XY:

725636

show subpopulations

African (AFR)

AF:

0.0342

AC:

1144

AN:

33460

American (AMR)

AF:

0.102

AC:

4554

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

3725

AN:

26102

East Asian (EAS)

AF:

0.00184

AC:

AN:

39662

South Asian (SAS)

AF:

0.103

AC:

8870

AN:

85986

European-Finnish (FIN)

AF:

0.270

AC:

14396

AN:

53312

Middle Eastern (MID)

AF:

0.140

AC:

805

AN:

5740

European-Non Finnish (NFE)

AF:

0.225

AC:

249450

AN:

1109728

Other (OTH)

AF:

0.180

AC:

10857

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

10336

20672

31008

41344

51680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8274

16548

24822

33096

41370

<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:

0.154

AC:

23449

AN:

152118

Hom.:

2448

Cov.:

AF XY:

0.154

AC XY:

11444

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0403

AC:

1672

AN:

41520

American (AMR)

AF:

0.139

AC:

2130

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

471

AN:

3466

East Asian (EAS)

AF:

0.00308

AC:

AN:

5190

South Asian (SAS)

AF:

0.102

AC:

494

AN:

4826

European-Finnish (FIN)

AF:

0.279

AC:

2950

AN:

10574

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.223

AC:

15183

AN:

67956

Other (OTH)

AF:

0.169

AC:

355

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

950

1901

2851

3802

4752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.183

Hom.:

5334

Bravo

AF:

0.138

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 23, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

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

- -

Feb 26, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:2

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

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

- -

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

Benign:1

Dec 23, 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

-0.80

CADD

Benign

5.4

(source)

DANN

Benign

0.72

PhyloP100

-0.43

Mutation Taster

=93/7

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