rs2869577

Variant names:

• chr17-65199474-C-G
• rs2869577
• NM_003835.4:c.976+2233C>G

Variant summary

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

The NM_003835.4(RGS9):​c.976+2233C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 147,140 control chromosomes in the GnomAD database, including 2,192 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 (2192 hom., cov: 31)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 2 publications found

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]

RGS9 Gene-Disease associations (from GenCC):

• prolonged electroretinal response suppression 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• bradyopsia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003835.4. 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
	RGS9	NM_003835.4	MANE Select	c.976+2233C>G		intron	N/A	NP_003826.2	O75916-1
	RGS9	NM_001081955.3		c.967+2233C>G		intron	N/A	NP_001075424.1	O75916-5
	RGS9	NM_001165933.2		c.967+2233C>G		intron	N/A	NP_001159405.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	ENST00000262406.10	TSL:1 MANE Select	c.976+2233C>G		intron	N/A	ENSP00000262406.9	O75916-1
	RGS9	ENST00000449996.7	TSL:1	c.967+2233C>G		intron	N/A	ENSP00000396329.3	O75916-5
	RGS9	ENST00000443584.7	TSL:1	c.967+2233C>G		intron	N/A	ENSP00000405814.3	E9PD91

Frequencies

GnomAD3 genomes AF: 0.120 AC: 17684 AN: 147074 Hom.: 2189 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0342

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0774

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.0884

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 17716 AN: 147140 Hom.: 2192 Cov.: 31 AF XY: 0.124 AC XY: 8888 AN XY: 71550

African (AFR) AF: 0.264 AC: 10486 AN: 39742

American (AMR) AF: 0.234 AC: 3430 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 79 AN: 3418

East Asian (EAS) AF: 0.297 AC: 1491 AN: 5020

South Asian (SAS) AF: 0.0756 AC: 353 AN: 4670

European-Finnish (FIN) AF: 0.0286 AC: 264 AN: 9222

Middle Eastern (MID) AF: 0.0769 AC: 22 AN: 286

European-Non Finnish (NFE) AF: 0.0204 AC: 1372 AN: 67184

Other (OTH) AF: 0.0914 AC: 188 AN: 2058

Alfa AF: 0.0790 Hom.: 163

Bravo AF: 0.146

Asia WGS AF: 0.225 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.46
PhyloP100		-1.3
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: rs2869577; hg19: chr17-63195592;