5-90627624-A-G

Position:

chr5-90627624-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_032119.4(ADGRV1):c.1086A>G(p.Leu362=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,613,936 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 15 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:10

Conservation

PhyloP100: -0.207

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-90627624-A-G is Benign according to our data. Variant chr5-90627624-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158643.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=4}. Variant chr5-90627624-A-G is described in Lovd as [Likely_benign]. Variant chr5-90627624-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.207 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00223 (3255/1461652) while in subpopulation SAS AF= 0.00787 (679/86254). AF 95% confidence interval is 0.00738. There are 15 homozygotes in gnomad4_exome. There are 1814 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 15 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.1086A>G	p.Leu362=	synonymous_variant	7/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.1086A>G	p.Leu362=	synonymous_variant	7/90	1	NM_032119.4	P1	Q8WXG9-1
ADGRV1	ENST00000640281.1 linkuse as main transcript	n.1145A>G		non_coding_transcript_exon_variant	7/7	1
ADGRV1	ENST00000640083.1 linkuse as main transcript	n.791A>G		non_coding_transcript_exon_variant	5/6	5
ADGRV1	ENST00000640109.1 linkuse as main transcript	n.1182A>G		non_coding_transcript_exon_variant	7/9	5

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00238

AC:

593

AN:

249118

Hom.:

AF XY:

0.00300

AC XY:

406

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00765

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00223

AC:

3255

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1814

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00787

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00139

AC:

212

AN:

152284

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00344

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	ADGRV1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 17, 2019	- -

not specified

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 10, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 20, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 18, 2016	Leu362Leu in Exon 07 of GPR98: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.8% (125/16500) of S outh Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs186639101). -

Usher syndrome type 2C

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

ADGRV1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.7

DANN

Benign

0.67

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