chr17-65218385-A-T

Position:

• chr17-65218385-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.1408-6617A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,304 control chromosomes in the GnomAD database, including 723 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 0.049 (723 hom., cov: 32)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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 = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS9	NM_003835.4	c.1408-6617A>T		intron_variant		ENST00000262406.10
RGS9	NM_001081955.3	c.1399-6617A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS9	ENST00000262406.10	c.1408-6617A>T		intron_variant		1	NM_003835.4	P4

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7439 AN: 152186 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0426

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

GnomAD4 genome AF: 0.0490 AC: 7468 AN: 152304 Hom.: 723 Cov.: 32 AF XY: 0.0552 AC XY: 4109 AN XY: 74484

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.00884 Hom.: 3

Bravo AF: 0.0614

Asia WGS AF: 0.204 AC: 707 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	2.0
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: rs1122079; hg19: chr17-63214503;