rs950692

Positions:

• chr5-90647616-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.3141A>G​(p.Ala1047Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,534 control chromosomes in the GnomAD database, including 17,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2067 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15096 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-90647616-A-G is Benign according to our data. Variant chr5-90647616-A-G is described in ClinVar as [Benign]. Clinvar id is 46310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90647616-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.3141A>G	p.Ala1047Ala	synonymous_variant	17/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.3141A>G	p.Ala1047Ala	synonymous_variant	17/90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403.1	c.444A>G	p.Ala148Ala	synonymous_variant	7/29	5		ENSP00000492531.1
ADGRV1	ENST00000504142.2	n.1907A>G		non_coding_transcript_exon_variant	11/14	5
ADGRV1	ENST00000639676.1	n.739A>G		non_coding_transcript_exon_variant	5/11	5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23922 AN: 152046 Hom.: 2056 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.165 AC: 41121 AN: 248978 Hom.: 3957 AF XY: 0.165 AC XY: 22268 AN XY: 135054

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.136 AC: 198756 AN: 1461370 Hom.: 15096 Cov.: 33 AF XY: 0.138 AC XY: 100544 AN XY: 726970

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.158 AC: 23966 AN: 152164 Hom.: 2067 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74386

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.173

Alfa AF: 0.136 Hom.: 3147

Bravo AF: 0.158

Asia WGS AF: 0.300 AC: 1040 AN: 3476

EpiCase AF: 0.128

EpiControl AF: 0.130

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

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	Feb 01, 2011	Ala1047Ala in exon 17 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction and is listed in dbSNP with an average heterozygous frequency of 33.3% (rs950692). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Usher syndrome type 2C Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.19
DANN	Benign	0.48

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: rs950692; hg19: chr5-89943433; COSMIC: COSV67978723;