rs7219245

Variant names:

• chr17-65120581-G-A
• rs7219245
• ENST00000635833.1:c.57+19539G>A

Variant summary

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

The ENST00000635833.1(RGS9):​c.57+19539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,996 control chromosomes in the GnomAD database, including 34,627 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 0.65 (34627 hom., cov: 32)
• Consequence: RGS9 ENST00000635833.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000635833.1	c.57+19539G>A		intron_variant	Intron 1 of 18	5		ENSP00000490658.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98751 AN: 151878 Hom.: 34628 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.650 AC: 98779 AN: 151996 Hom.: 34627 Cov.: 32 AF XY: 0.655 AC XY: 48657 AN XY: 74322

African (AFR) AF: 0.363 AC: 15015 AN: 41392

American (AMR) AF: 0.747 AC: 11400 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4754 AN: 5176

South Asian (SAS) AF: 0.754 AC: 3631 AN: 4818

European-Finnish (FIN) AF: 0.733 AC: 7752 AN: 10578

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51554 AN: 67992

Other (OTH) AF: 0.666 AC: 1404 AN: 2108

Alfa AF: 0.695 Hom.: 6681

Bravo AF: 0.637

Asia WGS AF: 0.823 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.46
PhyloP100		-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7219245; hg19: chr17-63116699;