rs17624033

chr5-90745693-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.10872A>G(p.Gln3624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,612,324 control chromosomes in the GnomAD database, including 1,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1489 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: 0.128

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=-0.6).
• BP6: Variant 5-90745693-A-G is Benign according to our data. Variant chr5-90745693-A-G is described in ClinVar as [Benign]. Clinvar id is 46252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745693-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0318 (4840/152296) while in subpopulation AMR AF= 0.0466 (713/15294). AF 95% confidence interval is 0.0438. There are 125 homozygotes in gnomad4. There are 2280 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 125 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.10872A>G	p.Gln3624=	synonymous_variant	52/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.10872A>G	p.Gln3624=	synonymous_variant	52/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4842 AN: 152178 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0713

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0502

GnomAD3 exomes AF: 0.0312 AC: 7750 AN: 248594 Hom.: 197 AF XY: 0.0317 AC XY: 4276 AN XY: 134892

Gnomad AFR exome AF: 0.00698

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.0171

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0434

Gnomad OTH exome AF: 0.0382

GnomAD4 exome AF: 0.0420 AC: 61301 AN: 1460028 Hom.: 1489 Cov.: 29 AF XY: 0.0413 AC XY: 30017 AN XY: 726416

Gnomad4 AFR exome AF: 0.00783

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0629

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0318 AC: 4840 AN: 152296 Hom.: 125 Cov.: 32 AF XY: 0.0306 AC XY: 2280 AN XY: 74460

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0713

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0450 Hom.: 285

Bravo AF: 0.0344

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0477

EpiControl AF: 0.0463

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 11, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 14, 2011	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 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:1 Other:1

not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	4.3
Dann	Benign	0.30
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: rs17624033; hg19: chr5-90041510;