6-153106571-C-G

Variant names:

• chr6-153106571-C-G
• rs4083914
• NM_012419.5:c.-26+24553G>C

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+24553G>C 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 151,180 control chromosomes in the GnomAD database, including 17,086 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 (17086 hom., cov: 29)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 13 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-26+24553G>C		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.20+24468G>C		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.8+18513G>C		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-26+23728G>C		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+24553G>C		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70563 AN: 151064 Hom.: 17082 Cov.: 29

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.467 AC: 70581 AN: 151180 Hom.: 17086 Cov.: 29 AF XY: 0.472 AC XY: 34834 AN XY: 73764

African (AFR) AF: 0.493 AC: 20286 AN: 41132

American (AMR) AF: 0.436 AC: 6642 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1733 AN: 3460

East Asian (EAS) AF: 0.853 AC: 4291 AN: 5030

South Asian (SAS) AF: 0.626 AC: 2997 AN: 4786

European-Finnish (FIN) AF: 0.443 AC: 4596 AN: 10374

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28644 AN: 67872

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.449 Hom.: 1942

Bravo AF: 0.465

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	-0.98
CADD	Benign	0.71
DANN	Benign	0.29
PhyloP100		-0.50
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: rs4083914; hg19: chr6-153427706; COSMIC: COSV52810806;