rs61730895

Positions:

chr10-84257984-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.47

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 links:

RGR (HGNC:):

RGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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]. Clinvar id is 100573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84257984-C-T is described in Lovd as [Benign]. Variant chr10-84257984-C-T is described in Lovd as [Likely_pathogenic].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGR	NM_001012720.2 linkuse as main transcript	c.722C>T	p.Ser241Phe	missense_variant	6/7	ENST00000652092.2	NP_001012738.1	P47804-1
RGR	NM_002921.4 linkuse as main transcript	c.734C>T	p.Ser245Phe	missense_variant	6/7		NP_002912.2	P47804-2A0A0S2Z498
RGR	NM_001012722.2 linkuse as main transcript	c.631-524C>T		intron_variant			NP_001012740.1	P47804-3A0A0S2Z494

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGR	ENST00000652092.2 linkuse as main transcript	c.722C>T	p.Ser241Phe	missense_variant	6/7		NM_001012720.2	ENSP00000498299.1		P47804-1

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

GnomAD3 exomes

AF:

0.0524

AC:

13161

AN:

251384

Hom.:

430

AF XY:

0.0524

AC XY:

7122

AN XY:

135862

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 SAS exome

AF:

0.0655

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

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.0811

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0692

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0402

Gnomad4 OTH exome

AF:

0.0454

GnomAD4 genome

AF:

0.0397

AC:

6041

AN:

152302

Hom.:

180

Cov.:

AF XY:

0.0413

AC XY:

3076

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.0710

Gnomad4 ASJ

AF:

0.0389

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0677

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.0393

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0373

Hom.:

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

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Mar 06, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

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

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over