rs3526

Variant names:

• chr10-84258704-A-G
• rs3526
• NM_001012720.2:c.*65A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.949
• Publications: 20 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 -20 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 VariationId is 301323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	NM_001012720.2	MANE Select	c.*65A>G		3_prime_UTR	Exon 7 of 7	NP_001012738.1
	RGR	NM_002921.4		c.*65A>G		3_prime_UTR	Exon 7 of 7	NP_002912.2
	RGR	NM_001012722.2		c.*65A>G		3_prime_UTR	Exon 6 of 6	NP_001012740.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGR	ENST00000652092.2	MANE Select	c.*65A>G		3_prime_UTR	Exon 7 of 7	ENSP00000498299.1
	RGR	ENST00000359452.9	TSL:1	c.*65A>G		3_prime_UTR	Exon 7 of 7	ENSP00000352427.4
	RGR	ENST00000358110.7	TSL:1	c.*65A>G		3_prime_UTR	Exon 6 of 6	ENSP00000350823.5

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

African (AFR) AF: 0.127 AC: 4225 AN: 33390

American (AMR) AF: 0.266 AC: 11794 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 6464 AN: 26032

East Asian (EAS) AF: 0.138 AC: 5476 AN: 39556

South Asian (SAS) AF: 0.144 AC: 12351 AN: 85998

European-Finnish (FIN) AF: 0.259 AC: 13331 AN: 51560

Middle Eastern (MID) AF: 0.215 AC: 1142 AN: 5316

European-Non Finnish (NFE) AF: 0.248 AC: 275075 AN: 1109464

Other (OTH) AF: 0.230 AC: 13834 AN: 60114

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

African (AFR) AF: 0.131 AC: 5408 AN: 41414

American (AMR) AF: 0.271 AC: 4132 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3470

East Asian (EAS) AF: 0.147 AC: 754 AN: 5116

South Asian (SAS) AF: 0.142 AC: 680 AN: 4776

European-Finnish (FIN) AF: 0.265 AC: 2791 AN: 10544

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17070 AN: 67866

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.133 Hom.: 260

Bravo AF: 0.211

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.70
PhyloP100		-0.95
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: rs3526; hg19: chr10-86018460;