rs685449

chr6-153023396-T-Achr6-153023396-T-C

Variant summary

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

The NM_012419.5(RGS17):c.444+866A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 507,118 control chromosomes in the GnomAD database, including 46,524 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 0.43 (13878 hom., cov: 32)
  • Exomes 𝑓: 0.42 (32646 hom.)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.444+866A>T		intron_variant		ENST00000206262.2
RGS17	XM_047418634.1	c.489+866A>T		intron_variant
RGS17	XM_047418635.1	c.477+866A>T		intron_variant
RGS17	XM_047418636.1	c.444+866A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.444+866A>T		intron_variant		1	NM_012419.5	P1
RGS17	ENST00000367225.6	c.444+866A>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64565 AN: 151956 Hom.: 13856 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.380

GnomAD3 exomes AF: 0.426 AC: 96726 AN: 227128 Hom.: 20907 AF XY: 0.429 AC XY: 53856 AN XY: 125620

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.463

Gnomad SAS exome AF: 0.534

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.424 AC: 150387 AN: 355044 Hom.: 32646 Cov.: 0 AF XY: 0.430 AC XY: 87935 AN XY: 204420

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.425 AC: 64635 AN: 152074 Hom.: 13878 Cov.: 32 AF XY: 0.428 AC XY: 31824 AN XY: 74332

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.386

Alfa AF: 0.380 Hom.: 6630

Bravo AF: 0.421

Asia WGS AF: 0.527 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.8
Dann	Benign	0.48

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: rs685449; hg19: chr6-153344531; COSMIC: COSV52806184;