chr17-65218385-A-T

Variant names:

• chr17-65218385-A-T
• rs1122079
• NM_003835.4:c.1408-6617A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

RGS9 Gene-Disease associations (from GenCC):

• prolonged electroretinal response suppression 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• bradyopsia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003835.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	NM_003835.4	MANE Select	c.1408-6617A>T		intron	N/A	NP_003826.2	O75916-1
	RGS9	NM_001081955.3		c.1399-6617A>T		intron	N/A	NP_001075424.1	O75916-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	ENST00000262406.10	TSL:1 MANE Select	c.1408-6617A>T		intron	N/A	ENSP00000262406.9	O75916-1
	RGS9	ENST00000449996.7	TSL:1	c.1399-6617A>T		intron	N/A	ENSP00000396329.3	O75916-5
	RGS9	ENST00000443584.7	TSL:1	c.1399-6617A>T		intron	N/A	ENSP00000405814.3	E9PD91

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

African (AFR) AF: 0.0106 AC: 440 AN: 41578

American (AMR) AF: 0.208 AC: 3188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1519 AN: 5180

South Asian (SAS) AF: 0.0737 AC: 356 AN: 4828

European-Finnish (FIN) AF: 0.0365 AC: 388 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1368 AN: 68024

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1122079; hg19: chr17-63214503;