5-90619108-T-G

Position:

chr5-90619108-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.380T>G(p.Leu127Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,468,956 control chromosomes in the GnomAD database, including 1,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 96 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1325 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.48

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=0.0067288876).

BP6

Variant 5-90619108-T-G is Benign according to our data. Variant chr5-90619108-T-G is described in ClinVar as [Benign]. Clinvar id is 46321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90619108-T-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0296 (4503/152262) while in subpopulation NFE AF= 0.0461 (3137/68012). AF 95% confidence interval is 0.0448. There are 96 homozygotes in gnomad4. There are 2129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 96 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.380T>G	p.Leu127Arg	missense_variant	4/90	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.380T>G	p.Leu127Arg	missense_variant	4/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4503

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0499

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0305

AC:

5556

AN:

182094

Hom.:

106

AF XY:

0.0303

AC XY:

2998

AN XY:

99032

show subpopulations

Gnomad AFR exome

AF:

0.00579

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00487

Gnomad FIN exome

AF:

0.0508

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0278

GnomAD4 exome

AF:

0.0414

AC:

54510

AN:

1316694

Hom.:

1325

Cov.:

AF XY:

0.0406

AC XY:

26335

AN XY:

649378

show subpopulations

Gnomad4 AFR exome

AF:

0.00596

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0000288

Gnomad4 SAS exome

AF:

0.00547

Gnomad4 FIN exome

AF:

0.0465

Gnomad4 NFE exome

AF:

0.0475

Gnomad4 OTH exome

AF:

0.0323

GnomAD4 genome

AF:

0.0296

AC:

4503

AN:

152262

Hom.:

Cov.:

AF XY:

0.0286

AC XY:

2129

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00811

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0499

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0261

Alfa

AF:

0.0406

Hom.:

233

Bravo

AF:

0.0266

TwinsUK

AF:

0.0494

AC:

183

ALSPAC

AF:

0.0415

AC:

160

ESP6500AA

AF:

0.00666

AC:

ESP6500EA

AF:

0.0459

AC:

373

ExAC

AF:

0.0293

AC:

3533

Asia WGS

AF:

0.00434

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 08, 2012	Leu127Arg in exon 4 of GPR98: This variant is not expected to have clinical sign ificance because it has been identified in 4.4% (289/6532) of European American chromosomes and 0.75% (22/2906) of African American chromosomes from a broad pop ulation by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/ ; dbSNP rs41311333). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 19, 2018	- -

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

0.34

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

.;T

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.9

.;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.0020

.;D

Polyphen

1.0

D;D

Vest4

0.31

MPC

0.34

ClinPred

0.012

GERP RS

5.4

Varity_R

0.75

gMVP

0.86

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