5-90756555-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.11682C>T(p.Pro3894Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,610,038 control chromosomes in the GnomAD database, including 178,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21400 hom., cov: 31)

Exomes 𝑓: 0.46 ( 157159 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.842

Publications

25 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.147).

BP6

Variant 5-90756555-C-T is Benign according to our data. Variant chr5-90756555-C-T is described in ClinVar as Benign. ClinVar VariationId is 46258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.842 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.11682C>T	p.Pro3894Pro	synonymous_variant	Exon 56 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.11682C>T	p.Pro3894Pro	synonymous_variant	Exon 56 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78972

AN:

151736

Hom.:

21360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.519

GnomAD2 exomes

AF:

0.487

AC:

121081

AN:

248730

AF XY:

0.474

show subpopulations

Gnomad AFR exome

AF:

0.676

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.460

AC:

670601

AN:

1458184

Hom.:

157159

Cov.:

AF XY:

0.456

AC XY:

330690

AN XY:

725490

show subpopulations

African (AFR)

AF:

0.672

AC:

22459

AN:

33416

American (AMR)

AF:

0.666

AC:

29736

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

9880

AN:

26118

East Asian (EAS)

AF:

0.504

AC:

19986

AN:

39638

South Asian (SAS)

AF:

0.420

AC:

36112

AN:

86078

European-Finnish (FIN)

AF:

0.448

AC:

23885

AN:

53358

Middle Eastern (MID)

AF:

0.456

AC:

2625

AN:

5758

European-Non Finnish (NFE)

AF:

0.449

AC:

497724

AN:

1108898

Other (OTH)

AF:

0.468

AC:

28194

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

17770

35540

53310

71080

88850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15170

30340

45510

60680

75850

<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:

0.521

AC:

79070

AN:

151854

Hom.:

21400

Cov.:

AF XY:

0.521

AC XY:

38671

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.668

AC:

27652

AN:

41418

American (AMR)

AF:

0.598

AC:

9135

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1314

AN:

3462

East Asian (EAS)

AF:

0.483

AC:

2487

AN:

5154

South Asian (SAS)

AF:

0.416

AC:

1999

AN:

4800

European-Finnish (FIN)

AF:

0.448

AC:

4704

AN:

10500

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.444

AC:

30134

AN:

67938

Other (OTH)

AF:

0.515

AC:

1086

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1832

3665

5497

7330

9162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.470

Hom.:

9394

Bravo

AF:

0.543

Asia WGS

AF:

0.477

AC:

1659

AN:

3478

EpiCase

AF:

0.447

EpiControl

AF:

0.446

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 29, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 22, 2015

Eurofins Ntd Llc (ga)

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

- -

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

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

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.8

(source)

DANN

Benign

0.24

PhyloP100

0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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