rs2279227

Variant names:

• chr10-84245117-T-C
• rs2279227
• NM_001012720.2:c.27T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012720.2(RGR):​c.27T>C​(p.Thr9Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,612,688 control chromosomes in the GnomAD database, including 213,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31003 hom., cov: 31)
  • Exomes 𝑓: 0.49 (182386 hom.)
• Consequence: RGR NM_001012720.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.01
• Publications: 33 publications found

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: SD, AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-84245117-T-C is Benign according to our data. Variant chr10-84245117-T-C is described in ClinVar as Benign. ClinVar VariationId is 285754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	NM_001012720.2	MANE Select	c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 7	NP_001012738.1	P47804-1
	RGR	NM_002921.4		c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 7	NP_002912.2
	RGR	NM_001012722.2		c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 6	NP_001012740.1	P47804-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	ENST00000652092.2	MANE Select	c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 7	ENSP00000498299.1	P47804-1
	RGR	ENST00000359452.9	TSL:1	c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 7	ENSP00000352427.4	P47804-2
	RGR	ENST00000358110.7	TSL:1	c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 6	ENSP00000350823.5	P47804-3

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92831 AN: 151802 Hom.: 30942 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.526 AC: 131682 AN: 250368 AF XY: 0.517

Gnomad AFR exome AF: 0.910

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.529

GnomAD4 exome AF: 0.494 AC: 721800 AN: 1460766 Hom.: 182386 Cov.: 47 AF XY: 0.494 AC XY: 358629 AN XY: 726662

African (AFR) AF: 0.919 AC: 30746 AN: 33458

American (AMR) AF: 0.584 AC: 26104 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12816 AN: 26128

East Asian (EAS) AF: 0.442 AC: 17520 AN: 39676

South Asian (SAS) AF: 0.513 AC: 44210 AN: 86202

European-Finnish (FIN) AF: 0.488 AC: 26024 AN: 53310

Middle Eastern (MID) AF: 0.554 AC: 3055 AN: 5516

European-Non Finnish (NFE) AF: 0.477 AC: 529814 AN: 1111448

Other (OTH) AF: 0.522 AC: 31511 AN: 60330

GnomAD4 genome AF: 0.612 AC: 92940 AN: 151922 Hom.: 31003 Cov.: 31 AF XY: 0.610 AC XY: 45258 AN XY: 74208

African (AFR) AF: 0.904 AC: 37479 AN: 41476

American (AMR) AF: 0.585 AC: 8937 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2394 AN: 5132

South Asian (SAS) AF: 0.515 AC: 2478 AN: 4810

European-Finnish (FIN) AF: 0.506 AC: 5323 AN: 10524

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32683 AN: 67924

Other (OTH) AF: 0.581 AC: 1222 AN: 2104

Alfa AF: 0.530 Hom.: 35508

Bravo AF: 0.629

Asia WGS AF: 0.530 AC: 1846 AN: 3478

EpiCase AF: 0.483

EpiControl AF: 0.478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis pigmentosa 44 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.52
PhyloP100		-1.0
PromoterAI		0.014	Neutral
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2279227; hg19: chr10-86004873; COSMIC: COSV63894051; COSMIC: COSV63894051;