rs80069610

Positions:

• chr5-90651617-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.3303A>G​(p.Val1101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,579,550 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (20 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.269

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=-0.55).
• BP6: Variant 5-90651617-A-G is Benign according to our data. Variant chr5-90651617-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 46315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90651617-A-G is described in Lovd as [Benign]. Variant chr5-90651617-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.269 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00163 (249/152330) while in subpopulation EAS AF= 0.0226 (117/5182). AF 95% confidence interval is 0.0193. There are 3 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.3303A>G	p.Val1101=	synonymous_variant	18/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.3303A>G	p.Val1101=	synonymous_variant	18/90	1	NM_032119.4	ENSP00000384582	P1
ADGRV1	ENST00000640403.1	c.606A>G	p.Val202=	synonymous_variant	8/29	5		ENSP00000492531
ADGRV1	ENST00000504142.2	n.2069A>G		non_coding_transcript_exon_variant	12/14	5
ADGRV1	ENST00000639676.1	n.901A>G		non_coding_transcript_exon_variant	6/11	5

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00262 AC: 642 AN: 245450 Hom.: 8 AF XY: 0.00247 AC XY: 329 AN XY: 133092

Gnomad AFR exome AF: 0.0000657

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0191

Gnomad SAS exome AF: 0.000539

Gnomad FIN exome AF: 0.00662

Gnomad NFE exome AF: 0.000861

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00113 AC: 1610 AN: 1427220 Hom.: 20 Cov.: 26 AF XY: 0.00107 AC XY: 764 AN XY: 711646

Gnomad4 AFR exome AF: 0.0000609

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0194

Gnomad4 SAS exome AF: 0.000533

Gnomad4 FIN exome AF: 0.00666

Gnomad4 NFE exome AF: 0.000291

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome AF: 0.00163 AC: 249 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74484

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00734

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000409 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.00810 AC: 29 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 12, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	Jun 08, 2012	- -

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2018	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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 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	-0.55
CADD	Benign	1.0
DANN	Benign	0.63
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: rs80069610; hg19: chr5-89947434; COSMIC: COSV67997835;