6-153050193-C-T

Position:

• chr6-153050193-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012419.5(RGS17):​c.-25-6150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,930 control chromosomes in the GnomAD database, including 11,990 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 0.39 (11990 hom., cov: 33)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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

Verdict is Benign. Variant got -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 = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS17	NM_012419.5	c.-25-6150G>A		intron_variant		ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.21-6150G>A		intron_variant			XP_047274590.1
RGS17	XM_047418635.1	c.9-6150G>A		intron_variant			XP_047274591.1
RGS17	XM_047418636.1	c.-25-6150G>A		intron_variant			XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.-25-6150G>A		intron_variant		1	NM_012419.5	ENSP00000206262	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58509 AN: 151812 Hom.: 11964 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.386 AC: 58585 AN: 151930 Hom.: 11990 Cov.: 33 AF XY: 0.390 AC XY: 28993 AN XY: 74274

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.368

Alfa AF: 0.350 Hom.: 1647

Bravo AF: 0.390

Asia WGS AF: 0.508 AC: 1760 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7761503; hg19: chr6-153371328;