chr5-90694507-A-G

Position:

chr5-90694507-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.7751A>G(p.Asn2584Ser) variant causes a missense change. The variant allele was found at a frequency of 0.669 in 1,613,680 control chromosomes in the GnomAD database, including 366,238 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42791 hom., cov: 32)

Exomes 𝑓: 0.66 ( 323447 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 6.65

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:

ADGRV1 (HGNC:):

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.266668E-7).

BP6

Variant 5-90694507-A-G is Benign according to our data. Variant chr5-90694507-A-G is described in ClinVar as [Benign]. Clinvar id is 46379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90694507-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.7751A>G	p.Asn2584Ser	missense_variant	33/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.7751A>G	p.Asn2584Ser	missense_variant	33/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112460

AN:

152022

Hom.:

42715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.711

AC:

177017

AN:

249062

Hom.:

63809

AF XY:

0.702

AC XY:

94801

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.826

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.801

Gnomad SAS exome

AF:

0.721

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.662

AC:

967644

AN:

1461540

Hom.:

323447

Cov.:

AF XY:

0.662

AC XY:

481104

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.916

Gnomad4 AMR exome

AF:

0.821

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.818

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.740

AC:

112590

AN:

152140

Hom.:

42791

Cov.:

AF XY:

0.742

AC XY:

55186

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.911

Gnomad4 AMR

AF:

0.774

Gnomad4 ASJ

AF:

0.669

Gnomad4 EAS

AF:

0.813

Gnomad4 SAS

AF:

0.724

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.747

Alfa

AF:

0.668

Hom.:

84471

Bravo

AF:

0.760

TwinsUK

AF:

0.630

AC:

2335

ALSPAC

AF:

0.649

AC:

2501

ESP6500AA

AF:

0.915

AC:

3558

ESP6500EA

AF:

0.645

AC:

5356

ExAC

AF:

0.709

AC:

85654

Asia WGS

AF:

0.809

AC:

2813

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.649

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 19, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Usher syndrome type 2C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.029

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.25

DEOGEN2

Benign

0.095

T;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.19

.;T;T

MetaRNN

Benign

8.3e-7

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.46

PROVEAN

Benign

1.7

.;N;.

REVEL

Benign

0.15

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.019

MPC

0.041

ClinPred

0.013

GERP RS

5.9

Varity_R

0.10

gMVP

0.16

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