rs150549897

Positions:

chr5-90712327-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_032119.4(ADGRV1):c.9083A>G(p.Asn3028Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000156 in 1,557,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.94

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008969128).

BP6

Variant 5-90712327-A-G is Benign according to our data. Variant chr5-90712327-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197473.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr5-90712327-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.9083A>G	p.Asn3028Ser	missense_variant	42/90	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.9083A>G	p.Asn3028Ser	missense_variant	42/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000217

AC:

AN:

179420

Hom.:

AF XY:

0.000168

AC XY:

AN XY:

95336

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.0000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000296

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000876

AC:

123

AN:

1404692

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

694276

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.0000265

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000265

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.000584

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152338

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.000903

ESP6500AA

AF:

0.00362

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 17, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 11, 2014	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 24, 2016

p.Asn3028Ser in exon 42 of GPR98: This variant is not expected to have clinical significance because it has been identified in 0.6% (18/2968) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs150549897). -

ADGRV1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.92

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.37

.;N

REVEL

Benign

0.090

Sift

Benign

0.41

.;T

Sift4G

Uncertain

0.034

.;D

Polyphen

0.028

B;B

Vest4

0.17

MVP

0.40

MPC

0.041

ClinPred

0.027

GERP RS

5.8

Varity_R

0.035

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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