rs41303346

chr5-90675436-G-Achr5-90675436-G-T

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.5304G>A(p.Glu1768=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,612,602 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (20 hom., cov: 32)
  • Exomes 𝑓: 0.019 (312 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.370

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=-0.7).
• BP6: Variant 5-90675436-G-A is Benign according to our data. Variant chr5-90675436-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90675436-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2026/152240) while in subpopulation NFE AF= 0.0209 (1420/68016). AF 95% confidence interval is 0.02. There are 20 homozygotes in gnomad4. There are 924 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.5304G>A	p.Glu1768=	synonymous_variant	24/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.5304G>A	p.Glu1768=	synonymous_variant	24/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2026 AN: 152122 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00440

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0132 AC: 3259 AN: 247174 Hom.: 26 AF XY: 0.0133 AC XY: 1788 AN XY: 134046

Gnomad AFR exome AF: 0.00430

Gnomad AMR exome AF: 0.00942

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00298

Gnomad FIN exome AF: 0.0161

Gnomad NFE exome AF: 0.0195

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0190 AC: 27811 AN: 1460362 Hom.: 312 Cov.: 30 AF XY: 0.0185 AC XY: 13470 AN XY: 726352

Gnomad4 AFR exome AF: 0.00353

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00355

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.0221

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.0133 AC: 2026 AN: 152240 Hom.: 20 Cov.: 32 AF XY: 0.0124 AC XY: 924 AN XY: 74440

Gnomad4 AFR AF: 0.00438

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0176 Hom.: 19

Bravo AF: 0.0132

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	Apr 17, 2012	Glu1768Glu in exon 24 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, and has been identified in 2% (133/6694) of Eur opean American chromosomes and 0.5% (16/3782) of African American chromosomes in a broad population by the NHLBI Exome sequencing project (http://evs.gs.washing ton.edu/EVS/; dbSNP rs41303346). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 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. -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 22, 2023	- -

Usher syndrome type 2C Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	5.5
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs41303346; hg19: chr5-89971253;