10-84251987-G-T

Position:

• chr10-84251987-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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGR	NM_001012720.2	c.359-870G>T		intron_variant		ENST00000652092.2	NP_001012738.1
RGR	NM_002921.4	c.371-870G>T		intron_variant			NP_002912.2
RGR	NM_001012722.2	c.359-870G>T		intron_variant			NP_001012740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGR	ENST00000652092.2	c.359-870G>T		intron_variant			NM_001012720.2	ENSP00000498299.1

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.130

Alfa AF: 0.137 Hom.: 1568

Bravo AF: 0.125

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.60

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: rs17103281; hg19: chr10-86011743;