rs41304884

chr5-90815704-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):c.16164A>G(p.Arg5388=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.885

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.16164A>G	p.Arg5388=	synonymous_variant	75/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.16164A>G	p.Arg5388=	synonymous_variant	75/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2092 AN: 152162 Hom.: 17 Cov.: 32

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.: 47 AF XY: 0.0193 AC XY: 1883 AN XY: 97506

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.: 27 AF XY: 0.0182 AC XY: 12725 AN XY: 699588

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.: 17 Cov.: 32 AF XY: 0.0140 AC XY: 1043 AN XY: 74468

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.: 7

Bravo AF: 0.0129

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 27, 2013	- -

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

Invitae

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

Other links and lift over

dbSNP: rs41304884; hg19: chr5-90111521;