17-65120581-G-A

Position:

• chr17-65120581-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS9	ENST00000635833.1	c.57+19539G>A		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.666

Alfa AF: 0.704 Hom.: 6616

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7219245; hg19: chr17-63116699;