NM_001012720.2:c.631-1483G>A

Variant names:

• chr10-84256410-G-A
• rs4933317
• NM_001012720.2:c.631-1483G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012720.2(RGR):​c.631-1483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,996 control chromosomes in the GnomAD database, including 2,896 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 0.19 (2896 hom., cov: 32)
• Consequence: RGR NM_001012720.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 7 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: Unknown, SD, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	NM_001012720.2	MANE Select	c.631-1483G>A		intron	N/A	NP_001012738.1
	RGR	NM_002921.4		c.643-1483G>A		intron	N/A	NP_002912.2
	RGR	NM_001012722.2		c.630+1967G>A		intron	N/A	NP_001012740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	ENST00000652092.2	MANE Select	c.631-1483G>A		intron	N/A	ENSP00000498299.1
	RGR	ENST00000359452.9	TSL:1	c.643-1483G>A		intron	N/A	ENSP00000352427.4
	RGR	ENST00000358110.7	TSL:1	c.630+1967G>A		intron	N/A	ENSP00000350823.5

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29177 AN: 151876 Hom.: 2895 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.192 AC: 29208 AN: 151996 Hom.: 2896 Cov.: 32 AF XY: 0.195 AC XY: 14508 AN XY: 74290

African (AFR) AF: 0.193 AC: 8014 AN: 41446

American (AMR) AF: 0.231 AC: 3523 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3466

East Asian (EAS) AF: 0.150 AC: 777 AN: 5168

South Asian (SAS) AF: 0.131 AC: 630 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2502 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12426 AN: 67958

Other (OTH) AF: 0.192 AC: 404 AN: 2108

Alfa AF: 0.177 Hom.: 4168

Bravo AF: 0.192

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.77
PhyloP100		-1.3
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: rs4933317; hg19: chr10-86016166;