rs2279227

chr10-84245117-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012720.2(RGR):c.27T>C(p.Thr9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,612,688 control chromosomes in the GnomAD database, including 213,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31003 hom., cov: 31)
  • Exomes 𝑓: 0.49 (182386 hom.)
• Consequence: RGR NM_001012720.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.01

Genes affected

RGR (HGNC:9990): (retinal G protein coupled receptor) This gene encodes a putative retinal G-protein coupled receptor. The gene is a member of the opsin subfamily of the 7 transmembrane, G-protein coupled receptor 1 family. Like other opsins which bind retinaldehyde, it contains a conserved lysine residue in the seventh transmembrane domain. The protein acts as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. The reverse isomerization occurs with rhodopsin in retinal photoreceptor cells. The protein is exclusively expressed in tissue adjacent to retinal photoreceptor cells, the retinal pigment epithelium and Mueller cells. This gene may be associated with autosomal recessive and autosomal dominant retinitis pigmentosa (arRP and adRP, respectively). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-84245117-T-C is Benign according to our data. Variant chr10-84245117-T-C is described in ClinVar as [Benign]. Clinvar id is 285754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84245117-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGR	NM_001012720.2	c.27T>C	p.Thr9=	synonymous_variant	1/7	ENST00000652092.2
RGR	NM_002921.4	c.27T>C	p.Thr9=	synonymous_variant	1/7
RGR	NM_001012722.2	c.27T>C	p.Thr9=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGR	ENST00000652092.2	c.27T>C	p.Thr9=	synonymous_variant	1/7		NM_001012720.2	A1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92831 AN: 151802 Hom.: 30942 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.578

GnomAD3 exomes AF: 0.526 AC: 131682 AN: 250368 Hom.: 36259 AF XY: 0.517 AC XY: 69926 AN XY: 135356

Gnomad AFR exome AF: 0.910

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.507

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.529

GnomAD4 exome AF: 0.494 AC: 721800 AN: 1460766 Hom.: 182386 Cov.: 47 AF XY: 0.494 AC XY: 358629 AN XY: 726662

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.612 AC: 92940 AN: 151922 Hom.: 31003 Cov.: 31 AF XY: 0.610 AC XY: 45258 AN XY: 74208

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.581

Alfa AF: 0.517 Hom.: 27018

Bravo AF: 0.629

Asia WGS AF: 0.530 AC: 1846 AN: 3478

EpiCase AF: 0.483

EpiControl AF: 0.478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 27, 2016	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Retinitis pigmentosa 44 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa 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	-0.90
Cadd	Benign	0.58
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2279227; hg19: chr10-86004873; COSMIC: COSV63894051; COSMIC: COSV63894051;