rs35092519

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 46264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90778942-G-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.0239

AC:

5948

AN:

248854

Hom.:

118

AF XY:

0.0231

AC XY:

3114

AN XY:

134986

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 SAS exome

AF:

0.00693

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

Gnomad4 AFR exome

AF:

0.0652

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.0765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00628

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0352

AC:

5351

AN:

152196

Hom.:

123

Cov.:

AF XY:

0.0341

AC XY:

2535

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0658

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0827

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.0375

Alfa

AF:

0.0289

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

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. -

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

- -

Jun 23, 2017

Athena Diagnostics

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. -

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

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over