chr5-90778942-G-A

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.12927G>A(p.Ala4309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,416 control chromosomes in the GnomAD database, including 690 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. A4309A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.035 ( 123 hom., cov: 32)

Exomes 𝑓: 0.024 ( 567 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.17

Publications

2 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=-0.76).

BP6

Variant 5-90778942-G-A is Benign according to our data. Variant chr5-90778942-G-A is described in ClinVar as Benign. ClinVar VariationId is 46264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.12927G>A	p.Ala4309Ala	synonymous_variant	Exon 64 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.12927G>A	p.Ala4309Ala	synonymous_variant	Exon 64 of 90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000425867.3 link	c.1881G>A	p.Ala627Ala	synonymous_variant	Exon 12 of 38	5		ENSP00000392618.3	A0A1X7SBU6
ADGRV1	ENST00000640464.1 link	n.3346G>A		non_coding_transcript_exon_variant	Exon 21 of 21	5
ADGRV1	ENST00000639431.1 link	n.265+102733G>A		intron_variant	Intron 2 of 4	5		ENSP00000491057.1	A0A1W2PNS5

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5343

AN:

152078

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0379

GnomAD2 exomes

AF:

0.0239

AC:

5948

AN:

248854

AF XY:

0.0231

show subpopulations

Gnomad AFR exome

AF:

0.0650

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0771

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0257

GnomAD4 exome

AF:

0.0239

AC:

34922

AN:

1461220

Hom.:

567

Cov.:

AF XY:

0.0235

AC XY:

17106

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.0652

AC:

2182

AN:

33442

American (AMR)

AF:

0.0183

AC:

817

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0765

AC:

1997

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00628

AC:

542

AN:

86244

European-Finnish (FIN)

AF:

0.0182

AC:

974

AN:

53402

Middle Eastern (MID)

AF:

0.0340

AC:

196

AN:

5760

European-Non Finnish (NFE)

AF:

0.0238

AC:

26493

AN:

1111516

Other (OTH)

AF:

0.0285

AC:

1721

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1709

3418

5128

6837

8546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1010

2020

3030

4040

5050

<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:

0.0352

AC:

5351

AN:

152196

Hom.:

123

Cov.:

AF XY:

0.0341

AC XY:

2535

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0658

AC:

2734

AN:

41530

American (AMR)

AF:

0.0263

AC:

402

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0827

AC:

287

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00581

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0238

AC:

1616

AN:

68000

Other (OTH)

AF:

0.0375

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

258

517

775

1034

1292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0293

Hom.:

Bravo

AF:

0.0392

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0305

EpiControl

AF:

0.0307

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 23, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

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. -

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. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.76

CADD

Benign

0.046

(source)

DANN

Benign

0.56

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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