rs4933317

Positions:

• chr10-84256410-G-A
• chr10-84256410-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGR	NM_001012720.2	c.631-1483G>A		intron_variant		ENST00000652092.2
RGR	NM_001012722.2	c.630+1967G>A		intron_variant
RGR	NM_002921.4	c.643-1483G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGR	ENST00000652092.2	c.631-1483G>A		intron_variant			NM_001012720.2	A1

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.192

Alfa AF: 0.174 Hom.: 3187

Bravo AF: 0.192

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs4933317; hg19: chr10-86016166;