rs9916525

Positions:

• chr17-65215319-C-T

Variant summary

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

The ENST00000262406.10(RGS9):​c.1407+4714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,880 control chromosomes in the GnomAD database, including 18,621 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 0.41 (18621 hom., cov: 31)
• Consequence: RGS9 ENST00000262406.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS9	NM_003835.4	c.1407+4714C>T		intron_variant		ENST00000262406.10	NP_003826.2
RGS9	NM_001081955.3	c.1398+4714C>T		intron_variant			NP_001075424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000262406.10	c.1407+4714C>T		intron_variant		1	NM_003835.4	ENSP00000262406	P4

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62052 AN: 151762 Hom.: 18557 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.409 AC: 62183 AN: 151880 Hom.: 18621 Cov.: 31 AF XY: 0.407 AC XY: 30214 AN XY: 74230

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.387

Alfa AF: 0.299 Hom.: 1589

Bravo AF: 0.449

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.64

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: rs9916525; hg19: chr17-63211437;