10-84257984-C-T

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.722C>T(p.Ser241Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,614,066 control chromosomes in the GnomAD database, including 1,868 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 180 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1688 hom. )

Consequence

RGR
NM_001012720.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 1.47

Publications

14 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 (MetaRNN=0.0017181933).

BP6

Variant 10-84257984-C-T is Benign according to our data. Variant chr10-84257984-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 100573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012720.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RGR	NM_001012720.2	MANE Select	c.722C>T	p.Ser241Phe	missense	Exon 6 of 7	NP_001012738.1
RGR	NM_002921.4		c.734C>T	p.Ser245Phe	missense	Exon 6 of 7	NP_002912.2
RGR	NM_001012722.2		c.631-524C>T		intron	N/A	NP_001012740.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RGR	ENST00000652092.2	MANE Select	c.722C>T	p.Ser241Phe	missense	Exon 6 of 7	ENSP00000498299.1
RGR	ENST00000359452.9	TSL:1	c.734C>T	p.Ser245Phe	missense	Exon 6 of 7	ENSP00000352427.4
RGR	ENST00000358110.7	TSL:1	c.631-524C>T		intron	N/A	ENSP00000350823.5

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6042

AN:

152182

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0524

AC:

13161

AN:

251384

AF XY:

0.0524

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0829

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0444

AC:

64882

AN:

1461764

Hom.:

1688

Cov.:

AF XY:

0.0453

AC XY:

32966

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.0177

AC:

591

AN:

33478

American (AMR)

AF:

0.0811

AC:

3627

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0365

AC:

953

AN:

26134

East Asian (EAS)

AF:

0.110

AC:

4385

AN:

39698

South Asian (SAS)

AF:

0.0692

AC:

5973

AN:

86256

European-Finnish (FIN)

AF:

0.0339

AC:

1811

AN:

53392

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5768

European-Non Finnish (NFE)

AF:

0.0402

AC:

44689

AN:

1111928

Other (OTH)

AF:

0.0454

AC:

2744

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

3495

6990

10486

13981

17476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1782

3564

5346

7128

8910

<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:

0.0397

AC:

6041

AN:

152302

Hom.:

180

Cov.:

AF XY:

0.0413

AC XY:

3076

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0183

AC:

760

AN:

41578

American (AMR)

AF:

0.0710

AC:

1086

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

135

AN:

3472

East Asian (EAS)

AF:

0.123

AC:

639

AN:

5176

South Asian (SAS)

AF:

0.0677

AC:

327

AN:

4828

European-Finnish (FIN)

AF:

0.0305

AC:

324

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0393

AC:

2676

AN:

68010

Other (OTH)

AF:

0.0402

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

300

601

901

1202

1502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0400

Hom.:

280

Bravo

AF:

0.0411

TwinsUK

AF:

0.0421

AC:

156

ALSPAC

AF:

0.0366

AC:

141

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.0353

AC:

304

ExAC

AF:

0.0506

AC:

6148

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0374

EpiControl

AF:

0.0375

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

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

not specified

Benign:1

Aug 18, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely 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

Mar 06, 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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.59

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

PhyloP100

1.5

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.30

REVEL

Benign

0.10

Sift

Benign

0.71

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.15

MPC

0.13

ClinPred

0.0019

GERP RS

-0.63

gMVP

0.095

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over