10-84252957-C-T

Variant names:

• chr10-84252957-C-T
• rs1042454
• NM_001012720.2:c.459C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.38
• Publications: 25 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 -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.

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.459C>T	p.Tyr153Tyr	synonymous	Exon 4 of 7	NP_001012738.1	P47804-1
	RGR	NM_002921.4		c.471C>T	p.Tyr157Tyr	synonymous	Exon 4 of 7	NP_002912.2
	RGR	NM_001012722.2		c.459C>T	p.Tyr153Tyr	synonymous	Exon 4 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.459C>T	p.Tyr153Tyr	synonymous	Exon 4 of 7	ENSP00000498299.1	P47804-1
	RGR	ENST00000359452.9	TSL:1	c.471C>T	p.Tyr157Tyr	synonymous	Exon 4 of 7	ENSP00000352427.4	P47804-2
	RGR	ENST00000358110.7	TSL:1	c.459C>T	p.Tyr153Tyr	synonymous	Exon 4 of 6	ENSP00000350823.5	P47804-3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75651 AN: 151858 Hom.: 21461 Cov.: 32

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

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.: 50 AF XY: 0.378 AC XY: 274928 AN XY: 727112

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

GnomAD4 genome AF: 0.498 AC: 75731 AN: 151978 Hom.: 21496 Cov.: 32 AF XY: 0.500 AC XY: 37109 AN XY: 74272

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

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

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	-0.40
CADD	Benign	9.3
DANN	Benign	0.52
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042454; hg19: chr10-86012713; COSMIC: COSV63893663; COSMIC: COSV63893663;