rs1933258

Variant names:

• chr6-153056672-G-C
• rs1933258
• NM_012419.5:c.-25-12629C>G

Variant summary

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

The NM_012419.5(RGS17):​c.-25-12629C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,962 control chromosomes in the GnomAD database, including 11,870 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 0.38 (11870 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 1 publications found

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.-25-12629C>G		intron	N/A	NP_036551.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.-25-12629C>G		intron	N/A	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58265 AN: 151844 Hom.: 11847 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.384 AC: 58336 AN: 151962 Hom.: 11870 Cov.: 32 AF XY: 0.388 AC XY: 28837 AN XY: 74242

African (AFR) AF: 0.495 AC: 20526 AN: 41472

American (AMR) AF: 0.386 AC: 5885 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3466

East Asian (EAS) AF: 0.618 AC: 3181 AN: 5150

South Asian (SAS) AF: 0.509 AC: 2452 AN: 4820

European-Finnish (FIN) AF: 0.350 AC: 3693 AN: 10544

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.300 AC: 20388 AN: 67936

Other (OTH) AF: 0.366 AC: 772 AN: 2112

Alfa AF: 0.346 Hom.: 1159

Bravo AF: 0.389

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1933258; hg19: chr6-153377807;