rs2292592

Positions:

• chr17-65208091-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003835.4(RGS9):​c.1289+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 915,430 control chromosomes in the GnomAD database, including 7,089 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 0.12 (2128 hom., cov: 32)
  • Exomes 𝑓: 0.062 (4961 hom.)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

Genes affected

RGS9 (HGNC:10004): (regulator of G protein signaling 9) This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G proteins in the rod and cone phototransduction cascades. Mutations in this gene result in bradyopsia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS9	NM_003835.4	c.1289+84A>G		intron_variant		ENST00000262406.10	NP_003826.2
RGS9	NM_001081955.3	c.1280+84A>G		intron_variant			NP_001075424.1
RGS9	NM_001165933.2	c.1280+84A>G		intron_variant			NP_001159405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000262406.10	c.1289+84A>G		intron_variant		1	NM_003835.4	ENSP00000262406.9

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17855 AN: 151926 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0893

GnomAD4 exome AF: 0.0617 AC: 47099 AN: 763386 Hom.: 4961 AF XY: 0.0581 AC XY: 23547 AN XY: 405096

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.0709

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0738

GnomAD4 genome AF: 0.118 AC: 17901 AN: 152044 Hom.: 2128 Cov.: 32 AF XY: 0.122 AC XY: 9044 AN XY: 74294

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.105 Hom.: 306

Bravo AF: 0.140

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.56

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: rs2292592; hg19: chr17-63204209;