rs41304884

Positions:

chr5-90815704-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032119.4(ADGRV1):c.16164A>G(p.Arg5388Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,566,476 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 17 hom., cov: 32)

Exomes 𝑓: 0.017 ( 312 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.885

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-90815704-A-G is Benign according to our data. Variant chr5-90815704-A-G is described in ClinVar as [Benign]. Clinvar id is 46283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90815704-A-G is described in Lovd as [Likely_benign]. Variant chr5-90815704-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.885 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0137 (2087/152280) while in subpopulation SAS AF= 0.0483 (233/4826). AF 95% confidence interval is 0.0432. There are 17 homozygotes in gnomad4. There are 1043 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.16164A>G	p.Arg5388Arg	synonymous_variant	75/90	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.16164A>G	p.Arg5388Arg	synonymous_variant	75/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2092

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0484

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0171

AC:

3139

AN:

184080

Hom.:

AF XY:

0.0193

AC XY:

1883

AN XY:

97506

show subpopulations

Gnomad AFR exome

AF:

0.00873

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00867

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0460

Gnomad FIN exome

AF:

0.00888

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0172

AC:

24315

AN:

1414196

Hom.:

312

Cov.:

AF XY:

0.0182

AC XY:

12725

AN XY:

699588

show subpopulations

Gnomad4 AFR exome

AF:

0.00857

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00765

Gnomad4 EAS exome

AF:

0.0000796

Gnomad4 SAS exome

AF:

0.0462

Gnomad4 FIN exome

AF:

0.00836

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0179

GnomAD4 genome

AF:

0.0137

AC:

2087

AN:

152280

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0483

Gnomad4 FIN

AF:

0.00923

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Apr 30, 2012	Arg5388Arg in exon 75 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 0.2% (13/6503) of Europe an American chromosomes and 0.8% (27/3116) of African American chromosomes from a broad population by the NHLBI Exome sequencing project (http://evs.gs.washingt on.edu/EVS/; dbSNP rs41304884), and is reported as benign (Le Quesne Stabel 201 2). -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 27, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 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. -

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.65

DANN

Benign

0.38

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