5-90658032-C-T

Position:

chr5-90658032-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032119.4(ADGRV1):c.4506C>T(p.Pro1502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,613,504 control chromosomes in the GnomAD database, including 4,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 350 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4453 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.04

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 5-90658032-C-T is Benign according to our data. Variant chr5-90658032-C-T is described in ClinVar as [Benign]. Clinvar id is 46329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90658032-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 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.4506C>T	p.Pro1502=	synonymous_variant	21/90	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.4506C>T	p.Pro1502=	synonymous_variant	21/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1
ADGRV1	ENST00000640403.1 linkuse as main transcript	c.1797C>T	p.Pro599=	synonymous_variant	11/29	5		ENSP00000492531
ADGRV1	ENST00000639676.1 linkuse as main transcript	n.2104C>T		non_coding_transcript_exon_variant	9/11	5
ADGRV1	ENST00000639473.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9011

AN:

151890

Hom.:

352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0602

Gnomad ASJ

AF:

0.0851

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0605

GnomAD3 exomes

AF:

0.0674

AC:

16783

AN:

249156

Hom.:

710

AF XY:

0.0719

AC XY:

9719

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.0859

Gnomad EAS exome

AF:

0.00484

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0462

Gnomad NFE exome

AF:

0.0814

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0739

AC:

107978

AN:

1461496

Hom.:

4453

Cov.:

AF XY:

0.0756

AC XY:

54937

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.0857

Gnomad4 EAS exome

AF:

0.00292

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0516

Gnomad4 NFE exome

AF:

0.0770

Gnomad4 OTH exome

AF:

0.0734

GnomAD4 genome

AF:

0.0592

AC:

9002

AN:

152008

Hom.:

350

Cov.:

AF XY:

0.0589

AC XY:

4379

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.0602

Gnomad4 ASJ

AF:

0.0851

Gnomad4 EAS

AF:

0.00561

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0802

Gnomad4 OTH

AF:

0.0594

Alfa

AF:

0.0759

Hom.:

465

Bravo

AF:

0.0556

EpiCase

AF:

0.0867

EpiControl

AF:

0.0883

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 16, 2010	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

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

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.7

DANN

Benign

0.74

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