5-90658032-C-T

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.4506C>T(p.Pro1502Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,613,504 control chromosomes in the GnomAD database, including 4,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1502P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.059 ( 350 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4453 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.04

Publications

16 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=-0.68).

BP6

Variant 5-90658032-C-T is Benign according to our data. Variant chr5-90658032-C-T is described in ClinVar as Benign. ClinVar VariationId is 46329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.4506C>T	p.Pro1502Pro	synonymous_variant	Exon 21 of 90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ADGRV1	ENST00000405460.9 link	c.4506C>T	p.Pro1502Pro	synonymous_variant	Exon 21 of 90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1 link	c.1797C>T	p.Pro599Pro	synonymous_variant	Exon 11 of 29	5		ENSP00000492531.1
ADGRV1	ENST00000639676.1 link	n.2104C>T		non_coding_transcript_exon_variant	Exon 9 of 11	5
ADGRV1	ENST00000639473.1 link	n.-36C>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9011

AN:

151890

Hom.:

352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.0851

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0605

GnomAD2 exomes

AF:

0.0674

AC:

16783

AN:

249156

AF XY:

0.0719

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.0859

Gnomad EAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.0462

Gnomad NFE exome

AF:

0.0814

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0739

AC:

107978

AN:

1461496

Hom.:

4453

Cov.:

AF XY:

0.0756

AC XY:

54937

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.0223

AC:

748

AN:

33480

American (AMR)

AF:

0.0449

AC:

2007

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0857

AC:

2239

AN:

26122

East Asian (EAS)

AF:

0.00292

AC:

116

AN:

39692

South Asian (SAS)

AF:

0.109

AC:

9432

AN:

86190

European-Finnish (FIN)

AF:

0.0516

AC:

2753

AN:

53398

Middle Eastern (MID)

AF:

0.104

AC:

598

AN:

5768

European-Non Finnish (NFE)

AF:

0.0770

AC:

85653

AN:

1111762

Other (OTH)

AF:

0.0734

AC:

4432

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

5211

10422

15632

20843

26054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3078

6156

9234

12312

15390

<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:

0.0592

AC:

9002

AN:

152008

Hom.:

350

Cov.:

AF XY:

0.0589

AC XY:

4379

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0254

AC:

1055

AN:

41480

American (AMR)

AF:

0.0602

AC:

919

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0851

AC:

295

AN:

3468

East Asian (EAS)

AF:

0.00561

AC:

AN:

5172

South Asian (SAS)

AF:

0.112

AC:

539

AN:

4802

European-Finnish (FIN)

AF:

0.0488

AC:

515

AN:

10550

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0802

AC:

5450

AN:

67950

Other (OTH)

AF:

0.0594

AC:

125

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

413

825

1238

1650

2063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0743

Hom.:

580

Bravo

AF:

0.0556

EpiCase

AF:

0.0867

EpiControl

AF:

0.0883

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 16, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 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. -

not provided

Benign:2Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

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

- -

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

-0.68

CADD

Benign

4.7

(source)

DANN

Benign

0.74

PhyloP100

-1.0

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