6-153090120-C-T

Variant names:

• chr6-153090120-C-T
• rs685826
• NM_012419.5:c.-26+41004G>A

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+41004G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,906 control chromosomes in the GnomAD database, including 22,452 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 0.54 (22452 hom., cov: 31)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 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+41004G>A		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+41004G>A		intron	N/A	ENSP00000206262.1	Q9UGC6
	RGS17	ENST00000914255.1		c.-26+41004G>A		intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82035 AN: 151788 Hom.: 22438 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.540 AC: 82095 AN: 151906 Hom.: 22452 Cov.: 31 AF XY: 0.540 AC XY: 40104 AN XY: 74214

African (AFR) AF: 0.483 AC: 19994 AN: 41396

American (AMR) AF: 0.549 AC: 8396 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2718 AN: 5154

South Asian (SAS) AF: 0.630 AC: 3036 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5437 AN: 10522

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38532 AN: 67954

Other (OTH) AF: 0.558 AC: 1176 AN: 2108

Alfa AF: 0.547 Hom.: 17326

Bravo AF: 0.540

Asia WGS AF: 0.614 AC: 2131 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.37
PhyloP100		-0.042
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: rs685826; hg19: chr6-153411255;