rs6901126

Variant names:

• chr6-153118927-T-C
• rs6901126
• NM_012419.5:c.-26+12197A>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+12197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,002 control chromosomes in the GnomAD database, including 16,245 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 0.45 (16245 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 12 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 = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-26+12197A>G		intron_variant	Intron 1 of 4	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.20+12112A>G		intron_variant	Intron 1 of 4		XP_047274590.1
RGS17	XM_047418635.1	c.8+6157A>G		intron_variant	Intron 1 of 4		XP_047274591.1
RGS17	XM_047418636.1	c.-26+11372A>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+12197A>G		intron_variant	Intron 1 of 4	1	NM_012419.5	ENSP00000206262.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68935 AN: 151884 Hom.: 16246 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.454 AC: 68949 AN: 152002 Hom.: 16245 Cov.: 32 AF XY: 0.460 AC XY: 34159 AN XY: 74288

African (AFR) AF: 0.449 AC: 18603 AN: 41454

American (AMR) AF: 0.430 AC: 6573 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4379 AN: 5166

South Asian (SAS) AF: 0.627 AC: 3020 AN: 4820

European-Finnish (FIN) AF: 0.441 AC: 4658 AN: 10556

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28622 AN: 67936

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.431 Hom.: 6847

Bravo AF: 0.450

Asia WGS AF: 0.657 AC: 2278 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	2.3
DANN	Benign	0.75
PhyloP100		-0.36
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: rs6901126; hg19: chr6-153440062; COSMIC: COSV52810970;