10-84252957-C-T

Position:

chr10-84252957-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 197174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-84252957-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
RGR	NM_001012720.2 linkuse as main transcript	c.459C>T	p.Tyr153Tyr	synonymous_variant	4/7	ENST00000652092.2	NP_001012738.1	P47804-1
RGR	NM_002921.4 linkuse as main transcript	c.471C>T	p.Tyr157Tyr	synonymous_variant	4/7		NP_002912.2	P47804-2A0A0S2Z498
RGR	NM_001012722.2 linkuse as main transcript	c.459C>T	p.Tyr153Tyr	synonymous_variant	4/6		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.459C>T	p.Tyr153Tyr	synonymous_variant	4/7		NM_001012720.2	ENSP00000498299.1		P47804-1

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

GnomAD3 exomes

AF:

0.415

AC:

104335

AN:

251218

Hom.:

23561

AF XY:

0.404

AC XY:

54808

AN XY:

135768

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 SAS exome

AF:

0.381

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

Gnomad4 AFR exome

AF:

0.807

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.498

AC:

75731

AN:

151978

Hom.:

21496

Cov.:

AF XY:

0.500

AC XY:

37109

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.468

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.396

Hom.:

13732

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 25, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

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	-	- -

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

-0.40

CADD

Benign

9.3

DANN

Benign

0.52

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