Genetic Variant RGR:c.359-870G>T (chr10-84251987-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012720.2(RGR):c.359-870G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,182 control chromosomes in the GnomAD database, including 1,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1260 hom., cov: 32)

Consequence

RGR
NM_001012720.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0690

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RGR	NM_001012720.2 link	c.359-870G>T	intron_variant	Intron 3 of 6	ENST00000652092.2	NP_001012738.1
RGR	NM_002921.4 link	c.371-870G>T	intron_variant	Intron 3 of 6		NP_002912.2
RGR	NM_001012722.2 link	c.359-870G>T	intron_variant	Intron 3 of 5		NP_001012740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGR	ENST00000652092.2 link	c.359-870G>T		intron_variant	Intron 3 of 6		NM_001012720.2	ENSP00000498299.1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19462

AN:

152064

Hom.:

1259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.0953

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.128

AC:

19474

AN:

152182

Hom.:

1260

Cov.:

AF XY:

0.127

AC XY:

9483

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.117

AC:

4879

AN:

41526

American (AMR)

AF:

0.0952

AC:

1455

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

684

AN:

5176

South Asian (SAS)

AF:

0.160

AC:

773

AN:

4824

European-Finnish (FIN)

AF:

0.139

AC:

1471

AN:

10594

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9278

AN:

67992

Other (OTH)

AF:

0.130

AC:

274

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

884

1768

2653

3537

4421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.135

Hom.:

2251

Bravo

AF:

0.125

Asia WGS

AF:

0.142

AC:

495

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.1

(source)

DANN

Benign

0.60

PhyloP100

0.069

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over