rs2292593

chr17-65201802-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003835.4(RGS9):c.977-191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,170 control chromosomes in the GnomAD database, including 5,080 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 (5080 hom., cov: 32)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS9	NM_003835.4	c.977-191T>C		intron_variant		ENST00000262406.10
RGS9	NM_001081955.3	c.968-191T>C		intron_variant
RGS9	NM_001165933.2	c.968-191T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS9	ENST00000262406.10	c.977-191T>C		intron_variant		1	NM_003835.4	P4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30342 AN: 152050 Hom.: 5063 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.200 AC: 30412 AN: 152170 Hom.: 5080 Cov.: 32 AF XY: 0.201 AC XY: 14921 AN XY: 74406

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0936 Hom.: 2573

Bravo AF: 0.229

Asia WGS AF: 0.273 AC: 949 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.80
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292593; hg19: chr17-63197920; COSMIC: COSV52227421;