rs3526

Positions:

• chr10-84258704-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012720.2(RGR):​c.*65A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,607,596 control chromosomes in the GnomAD database, including 45,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3752 hom., cov: 31)
  • Exomes 𝑓: 0.24 (41727 hom.)
• Consequence: RGR NM_001012720.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.949

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-84258704-A-G is Benign according to our data. Variant chr10-84258704-A-G is described in ClinVar as [Benign]. Clinvar id is 301323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGR	NM_001012720.2	c.*65A>G		3_prime_UTR_variant	7/7	ENST00000652092.2
RGR	NM_001012722.2	c.*65A>G		3_prime_UTR_variant	6/6
RGR	NM_002921.4	c.*65A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGR	ENST00000652092.2	c.*65A>G		3_prime_UTR_variant	7/7		NM_001012720.2	A1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32487 AN: 151636 Hom.: 3747 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.236 AC: 343692 AN: 1455842 Hom.: 41727 Cov.: 31 AF XY: 0.235 AC XY: 169829 AN XY: 724176

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.214 AC: 32505 AN: 151754 Hom.: 3752 Cov.: 31 AF XY: 0.216 AC XY: 15987 AN XY: 74144

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.226

Alfa AF: 0.133 Hom.: 260

Bravo AF: 0.211

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.70

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: rs3526; hg19: chr10-86018460;