chr6-153109316-G-C

Variant names:

• chr6-153109316-G-C
• rs6931160
• NM_012419.5:c.-26+21808C>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+21808C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,946 control chromosomes in the GnomAD database, including 17,230 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 0.47 (17230 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	NM_012419.5	MANE Select	c.-26+21808C>G		intron	N/A	NP_036551.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.-26+21808C>G		intron	N/A	ENSP00000206262.1	Q9UGC6
	RGS17	ENST00000914255.1		c.-26+21808C>G		intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70999 AN: 151828 Hom.: 17227 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.467 AC: 71016 AN: 151946 Hom.: 17230 Cov.: 32 AF XY: 0.473 AC XY: 35131 AN XY: 74260

African (AFR) AF: 0.493 AC: 20437 AN: 41440

American (AMR) AF: 0.437 AC: 6674 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4401 AN: 5172

South Asian (SAS) AF: 0.628 AC: 3021 AN: 4812

European-Finnish (FIN) AF: 0.444 AC: 4681 AN: 10546

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28666 AN: 67930

Other (OTH) AF: 0.475 AC: 999 AN: 2104

Alfa AF: 0.450 Hom.: 1945

Bravo AF: 0.465

Asia WGS AF: 0.662 AC: 2296 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	5.2
DANN	Benign	0.38
PhyloP100		0.35
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: rs6931160; hg19: chr6-153430451; COSMIC: COSV52810841;