rs8070231

Variant names:

• chr17-65198827-A-G
• rs8070231
• NM_003835.4:c.976+1586A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-65198827-A-G
• chr17-65198827-A-T

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+1586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,164 control chromosomes in the GnomAD database, including 5,236 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 0.20 (5236 hom., cov: 32)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 7 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: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 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+1586A>G		intron	N/A	NP_003826.2
	RGS9	NM_001081955.3		c.967+1586A>G		intron	N/A	NP_001075424.1
	RGS9	NM_001165933.2		c.967+1586A>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+1586A>G		intron	N/A	ENSP00000262406.9
	RGS9	ENST00000449996.7	TSL:1	c.967+1586A>G		intron	N/A	ENSP00000396329.3
	RGS9	ENST00000443584.7	TSL:1	c.967+1586A>G		intron	N/A	ENSP00000405814.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30619 AN: 152046 Hom.: 5219 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.202 AC: 30691 AN: 152164 Hom.: 5236 Cov.: 32 AF XY: 0.202 AC XY: 15037 AN XY: 74412

African (AFR) AF: 0.437 AC: 18129 AN: 41460

American (AMR) AF: 0.293 AC: 4483 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0472 AC: 164 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1659 AN: 5178

South Asian (SAS) AF: 0.128 AC: 616 AN: 4820

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10626

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4608 AN: 68002

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.123 Hom.: 524

Bravo AF: 0.232

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.75
PhyloP100		-0.056
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: rs8070231; hg19: chr17-63194945;