chr17-65136210-C-T

Variant names:

• chr17-65136210-C-T
• rs4791230
• ENST00000635833.1:c.58-17212C>T

Variant summary

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

The ENST00000635833.1(RGS9):​c.58-17212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,142 control chromosomes in the GnomAD database, including 44,128 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 0.76 (44128 hom., cov: 32)
• Consequence: RGS9 ENST00000635833.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635833.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	ENST00000635833.1	TSL:5	c.58-17212C>T		intron	N/A	ENSP00000490658.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114892 AN: 152024 Hom.: 44122 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.755 AC: 114927 AN: 152142 Hom.: 44128 Cov.: 32 AF XY: 0.761 AC XY: 56591 AN XY: 74390

African (AFR) AF: 0.617 AC: 25594 AN: 41464

American (AMR) AF: 0.810 AC: 12379 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2439 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4822 AN: 5190

South Asian (SAS) AF: 0.740 AC: 3568 AN: 4820

European-Finnish (FIN) AF: 0.859 AC: 9101 AN: 10594

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.802 AC: 54539 AN: 68000

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.782 Hom.: 5805

Bravo AF: 0.750

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.83
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs4791230; hg19: chr17-63132328;