rs8077696

Variant names:

• chr17-65196443-C-A
• rs8077696
• NM_003835.4:c.861-683C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-65196443-C-A
• chr17-65196443-C-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.861-683C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,102 control chromosomes in the GnomAD database, including 4,508 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 0.19 (4508 hom., cov: 32)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 9 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 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.861-683C>A		intron	N/A	NP_003826.2	O75916-1
	RGS9	NM_001081955.3		c.852-683C>A		intron	N/A	NP_001075424.1	O75916-5
	RGS9	NM_001165933.2		c.852-683C>A		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.861-683C>A		intron	N/A	ENSP00000262406.9	O75916-1
	RGS9	ENST00000449996.7	TSL:1	c.852-683C>A		intron	N/A	ENSP00000396329.3	O75916-5
	RGS9	ENST00000443584.7	TSL:1	c.852-683C>A		intron	N/A	ENSP00000405814.3	E9PD91

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28878 AN: 151984 Hom.: 4495 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.190 AC: 28938 AN: 152102 Hom.: 4508 Cov.: 32 AF XY: 0.191 AC XY: 14214 AN XY: 74364

African (AFR) AF: 0.397 AC: 16470 AN: 41462

American (AMR) AF: 0.290 AC: 4426 AN: 15278

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

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5154

South Asian (SAS) AF: 0.127 AC: 612 AN: 4818

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4604 AN: 68004

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.0969 Hom.: 882

Bravo AF: 0.219

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.24
PhyloP100		-1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs8077696;

hg19: chr17-63192561;