rs2279227

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001012720.2(RGR):c.27T>C(p.Thr9Thr) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.01

Publications

33 publications found

Variant links:

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]

RGR Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 44
Inheritance: Unknown, SD, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

RGR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 285754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
RGR	NM_001012720.2 link	c.27T>C	p.Thr9Thr	synonymous_variant	Exon 1 of 7	ENST00000652092.2	NP_001012738.1	P47804-1
RGR	NM_002921.4 link	c.27T>C	p.Thr9Thr	synonymous_variant	Exon 1 of 7		NP_002912.2	P47804-2A0A0S2Z498
RGR	NM_001012722.2 link	c.27T>C	p.Thr9Thr	synonymous_variant	Exon 1 of 6		NP_001012740.1	P47804-3A0A0S2Z494

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGR	ENST00000652092.2 link	c.27T>C	p.Thr9Thr	synonymous_variant	Exon 1 of 7		NM_001012720.2	ENSP00000498299.1		P47804-1

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92831

AN:

151802

Hom.:

30942

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.526

AC:

131682

AN:

250368

AF XY:

0.517

show subpopulations

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 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.:

AF XY:

0.494

AC XY:

358629

AN XY:

726662

show subpopulations

African (AFR)

AF:

0.919

AC:

30746

AN:

33458

American (AMR)

AF:

0.584

AC:

26104

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12816

AN:

26128

East Asian (EAS)

AF:

0.442

AC:

17520

AN:

39676

South Asian (SAS)

AF:

0.513

AC:

44210

AN:

86202

European-Finnish (FIN)

AF:

0.488

AC:

26024

AN:

53310

Middle Eastern (MID)

AF:

0.554

AC:

3055

AN:

5516

European-Non Finnish (NFE)

AF:

0.477

AC:

529814

AN:

1111448

Other (OTH)

AF:

0.522

AC:

31511

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

17925

35849

53774

71698

89623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15780

31560

47340

63120

78900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.612

AC:

92940

AN:

151922

Hom.:

31003

Cov.:

AF XY:

0.610

AC XY:

45258

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.904

AC:

37479

AN:

41476

American (AMR)

AF:

0.585

AC:

8937

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1713

AN:

3470

East Asian (EAS)

AF:

0.466

AC:

2394

AN:

5132

South Asian (SAS)

AF:

0.515

AC:

2478

AN:

4810

European-Finnish (FIN)

AF:

0.506

AC:

5323

AN:

10524

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.481

AC:

32683

AN:

67924

Other (OTH)

AF:

0.581

AC:

1222

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1594

3189

4783

6378

7972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.530

Hom.:

35508

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 27, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 44

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinitis pigmentosa

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.52

PhyloP100

-1.0

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over