chr10-84251987-G-T

Variant names:

• chr10-84251987-G-T
• rs17103281
• NM_001012720.2:c.359-870G>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 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.359-870G>T		intron	N/A	NP_001012738.1
	RGR	NM_002921.4		c.371-870G>T		intron	N/A	NP_002912.2
	RGR	NM_001012722.2		c.359-870G>T		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.359-870G>T		intron	N/A	ENSP00000498299.1
	RGR	ENST00000359452.9	TSL:1	c.371-870G>T		intron	N/A	ENSP00000352427.4
	RGR	ENST00000358110.7	TSL:1	c.359-870G>T		intron	N/A	ENSP00000350823.5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19462 AN: 152064 Hom.: 1259 Cov.: 32

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.: 32 AF XY: 0.127 AC XY: 9483 AN XY: 74404

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: 44 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9278 AN: 67992

Other (OTH) AF: 0.130 AC: 274 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		0.069
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: rs17103281; hg19: chr10-86011743;