rs8070231

Positions:

• chr17-65198827-A-G
• chr17-65198827-A-T

Variant summary

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

The NM_003835.4(RGS9):​c.976+1586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,164 control chromosomes in the GnomAD database, including 5,236 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 (5236 hom., cov: 32)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS9	NM_003835.4	c.976+1586A>G		intron_variant		ENST00000262406.10
RGS9	NM_001081955.3	c.967+1586A>G		intron_variant
RGS9	NM_001165933.2	c.967+1586A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS9	ENST00000262406.10	c.976+1586A>G		intron_variant		1	NM_003835.4	P4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30619 AN: 152046 Hom.: 5219 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.202 AC: 30691 AN: 152164 Hom.: 5236 Cov.: 32 AF XY: 0.202 AC XY: 15037 AN XY: 74412

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.0472

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.176

Alfa AF: 0.116 Hom.: 450

Bravo AF: 0.232

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.75

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: rs8070231; hg19: chr17-63194945;