chr5-90683881-C-T

Position:

chr5-90683881-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.5960C>T(p.Pro1987Leu) variant causes a missense change. The variant allele was found at a frequency of 0.345 in 1,612,646 control chromosomes in the GnomAD database, including 98,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8541 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90412 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.87

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=6.9624186E-4).

BP6

Variant 5-90683881-C-T is Benign according to our data. Variant chr5-90683881-C-T is described in ClinVar as [Benign]. Clinvar id is 46345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90683881-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 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.5960C>T	p.Pro1987Leu	missense_variant	28/90	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.5960C>T	p.Pro1987Leu	missense_variant	28/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49749

AN:

151850

Hom.:

8525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.364

AC:

89728

AN:

246604

Hom.:

17600

AF XY:

0.355

AC XY:

47483

AN XY:

133688

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.369

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.347

AC:

507360

AN:

1460678

Hom.:

90412

Cov.:

AF XY:

0.345

AC XY:

250508

AN XY:

726526

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.571

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.328

AC:

49779

AN:

151968

Hom.:

8541

Cov.:

AF XY:

0.330

AC XY:

24521

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.339

Hom.:

21998

Bravo

AF:

0.341

TwinsUK

AF:

0.332

AC:

1232

ALSPAC

AF:

0.350

AC:

1349

ESP6500AA

AF:

0.251

AC:

934

ESP6500EA

AF:

0.330

AC:

2712

ExAC

AF:

0.352

AC:

42478

Asia WGS

AF:

0.348

AC:

1210

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2014	- -
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 23, 2010	- -

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	- -

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. -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

.;T;T

MetaRNN

Benign

0.00070

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.5

.;D;.

REVEL

Benign

0.23

Sift

Benign

0.15

.;T;.

Sift4G

Uncertain

0.029

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.16

MPC

0.33

ClinPred

0.029

GERP RS

4.8

Varity_R

0.40

gMVP

0.61

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