6-153024174-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.444+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 805,852 control chromosomes in the GnomAD database, including 206,761 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 0.76 (45399 hom., cov: 32)
  • Exomes 𝑓: 0.70 (161362 hom.)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.444+88G>A		intron_variant		ENST00000206262.2
RGS17	XM_047418634.1	c.489+88G>A		intron_variant
RGS17	XM_047418635.1	c.477+88G>A		intron_variant
RGS17	XM_047418636.1	c.444+88G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.444+88G>A		intron_variant		1	NM_012419.5	P1
RGS17	ENST00000367225.6	c.444+88G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116087 AN: 152030 Hom.: 45324 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.700 AC: 457275 AN: 653704 Hom.: 161362 AF XY: 0.698 AC XY: 239988 AN XY: 343764

Gnomad4 AFR exome AF: 0.944

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.749

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.764 AC: 116224 AN: 152148 Hom.: 45399 Cov.: 32 AF XY: 0.764 AC XY: 56857 AN XY: 74378

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.717

Alfa AF: 0.650 Hom.: 3932

Bravo AF: 0.769

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.56
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs545323; hg19: chr6-153345309;