10-84252957-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001012720.2(RGR):c.459C>T(p.Tyr153Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,613,610 control chromosomes in the GnomAD database, including 131,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21496 hom., cov: 32)

Exomes 𝑓: 0.38 ( 109653 hom. )

Consequence

RGR
NM_001012720.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

Publications

25 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 10-84252957-C-T is Benign according to our data. Variant chr10-84252957-C-T is described in ClinVar as Benign. ClinVar VariationId is 197174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RGR	NM_001012720.2 link	c.459C>T	p.Tyr153Tyr	synonymous_variant	Exon 4 of 7	ENST00000652092.2	NP_001012738.1
RGR	NM_002921.4 link	c.471C>T	p.Tyr157Tyr	synonymous_variant	Exon 4 of 7		NP_002912.2
RGR	NM_001012722.2 link	c.459C>T	p.Tyr153Tyr	synonymous_variant	Exon 4 of 6		NP_001012740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGR	ENST00000652092.2 link	c.459C>T	p.Tyr153Tyr	synonymous_variant	Exon 4 of 7		NM_001012720.2	ENSP00000498299.1

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75651

AN:

151858

Hom.:

21461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.415

AC:

104335

AN:

251218

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.795

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.379

AC:

553919

AN:

1461632

Hom.:

109653

Cov.:

AF XY:

0.378

AC XY:

274928

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.807

AC:

27027

AN:

33472

American (AMR)

AF:

0.503

AC:

22507

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9516

AN:

26136

East Asian (EAS)

AF:

0.295

AC:

11722

AN:

39700

South Asian (SAS)

AF:

0.388

AC:

33448

AN:

86256

European-Finnish (FIN)

AF:

0.434

AC:

23167

AN:

53330

Middle Eastern (MID)

AF:

0.413

AC:

2376

AN:

5750

European-Non Finnish (NFE)

AF:

0.360

AC:

400115

AN:

1111898

Other (OTH)

AF:

0.398

AC:

24041

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

20296

40592

60888

81184

101480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12882

25764

38646

51528

64410

<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:

0.498

AC:

75731

AN:

151978

Hom.:

21496

Cov.:

AF XY:

0.500

AC XY:

37109

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.791

AC:

32775

AN:

41460

American (AMR)

AF:

0.468

AC:

7142

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1303

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1627

AN:

5146

South Asian (SAS)

AF:

0.384

AC:

1846

AN:

4806

European-Finnish (FIN)

AF:

0.460

AC:

4859

AN:

10558

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24663

AN:

67958

Other (OTH)

AF:

0.454

AC:

955

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1661

3322

4983

6644

8305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.435

Hom.:

22635

Bravo

AF:

0.513

Asia WGS

AF:

0.385

AC:

1341

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.358

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 25, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

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

-0.40

CADD

Benign

9.3

(source)

DANN

Benign

0.52

PhyloP100

1.4

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over