rs10514869

Variant names:

• chr17-65105140-A-G
• rs10514869
• ENST00000635833.1:c.57+4098A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638125.1(RGS9):​n.321+3844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 152,248 control chromosomes in the GnomAD database, including 578 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 0.036 (578 hom., cov: 32)
• Consequence: RGS9 ENST00000638125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 2 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC100507002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638125.1. 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
	LOC100507002	NR_110801.1		n.321+3844A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS9	ENST00000635833.1	TSL:5	c.57+4098A>G		intron	N/A	ENSP00000490658.1	A0A1B0GVU3
	RGS9	ENST00000582940.2	TSL:5	n.165+4098A>G		intron	N/A
	RGS9	ENST00000637818.1	TSL:5	n.303+3844A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5532 AN: 152130 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.00410

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0363 AC: 5527 AN: 152248 Hom.: 578 Cov.: 32 AF XY: 0.0427 AC XY: 3182 AN XY: 74446

African (AFR) AF: 0.00409 AC: 170 AN: 41552

American (AMR) AF: 0.0714 AC: 1092 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5166

South Asian (SAS) AF: 0.134 AC: 649 AN: 4832

European-Finnish (FIN) AF: 0.0511 AC: 542 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 888 AN: 68014

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0403 Hom.: 212

Bravo AF: 0.0354

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.77
PhyloP100		-0.55

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10514869;

hg19: chr17-63101258;