rs17544552

Positions:

chr5-90683701-C-T

Variant summary

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

The NM_032119.4(ADGRV1):c.5780C>T(p.Thr1927Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 1,613,630 control chromosomes in the GnomAD database, including 5,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1927T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.069 ( 418 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4596 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014486611).

BP6

Variant 5-90683701-C-T is Benign according to our data. Variant chr5-90683701-C-T is described in ClinVar as [Benign]. Clinvar id is 46339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90683701-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 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.5780C>T	p.Thr1927Met	missense_variant	28/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.5780C>T	p.Thr1927Met	missense_variant	28/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10530

AN:

152030

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0608

Gnomad ASJ

AF:

0.0807

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.0708

GnomAD3 exomes

AF:

0.0717

AC:

17827

AN:

248806

Hom.:

770

AF XY:

0.0760

AC XY:

10253

AN XY:

134950

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.0178

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0804

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0755

AC:

110293

AN:

1461482

Hom.:

4596

Cov.:

AF XY:

0.0773

AC XY:

56226

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0571

Gnomad4 AMR exome

AF:

0.0464

Gnomad4 ASJ exome

AF:

0.0822

Gnomad4 EAS exome

AF:

0.00993

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.0513

Gnomad4 NFE exome

AF:

0.0768

Gnomad4 OTH exome

AF:

0.0781

GnomAD4 genome

AF:

0.0692

AC:

10533

AN:

152148

Hom.:

418

Cov.:

AF XY:

0.0687

AC XY:

5110

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0594

Gnomad4 AMR

AF:

0.0607

Gnomad4 ASJ

AF:

0.0807

Gnomad4 EAS

AF:

0.0178

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.0487

Gnomad4 NFE

AF:

0.0798

Gnomad4 OTH

AF:

0.0696

Alfa

AF:

0.0790

Hom.:

1095

Bravo

AF:

0.0663

TwinsUK

AF:

0.0852

AC:

316

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.0600

AC:

234

ESP6500EA

AF:

0.0792

AC:

655

ExAC

AF:

0.0738

AC:

8916

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

EpiCase

AF:

0.0862

EpiControl

AF:

0.0873

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 14, 2013	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 30, 2010	- -

not provided

Benign:1Other:1

not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Usher syndrome type 2C

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

DANN

Benign

0.89

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.45

.;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.032

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.14

.;T;.

Polyphen

0.098

B;B;.

Vest4

0.021

MPC

0.081

ClinPred

0.016

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.47

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

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