6-153106382-G-C

Variant names:

• chr6-153106382-G-C
• rs9479510
• NM_012419.5:c.-26+24742C>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.-26+24742C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,240 control chromosomes in the GnomAD database, including 16,714 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 0.46 (16714 hom., cov: 29)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-26+24742C>G		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.20+24657C>G		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.8+18702C>G		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-26+23917C>G		intron_variant	Intron 1 of 4		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.-26+24742C>G		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69681 AN: 151120 Hom.: 16709 Cov.: 29

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.461 AC: 69701 AN: 151240 Hom.: 16714 Cov.: 29 AF XY: 0.467 AC XY: 34463 AN XY: 73814

African (AFR) AF: 0.490 AC: 20172 AN: 41156

American (AMR) AF: 0.431 AC: 6557 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3466

East Asian (EAS) AF: 0.854 AC: 4305 AN: 5042

South Asian (SAS) AF: 0.627 AC: 3011 AN: 4804

European-Finnish (FIN) AF: 0.440 AC: 4571 AN: 10400

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27971 AN: 67870

Other (OTH) AF: 0.469 AC: 984 AN: 2100

Alfa AF: 0.433 Hom.: 1776

Bravo AF: 0.459

Asia WGS AF: 0.661 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.4
DANN	Benign	0.72
PhyloP100		-0.18
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: rs9479510; hg19: chr6-153427517; COSMIC: COSV52810801;