rs3968480

chr6-153111431-G-Achr6-153111431-G-T

Variant summary

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

The NM_012419.5(RGS17):c.-26+19693C>T 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 152,050 control chromosomes in the GnomAD database, including 17,232 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 (17232 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.-26+19693C>T		intron_variant		ENST00000206262.2
RGS17	XM_047418634.1	c.20+19608C>T		intron_variant
RGS17	XM_047418635.1	c.8+13653C>T		intron_variant
RGS17	XM_047418636.1	c.-26+18868C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.-26+19693C>T		intron_variant		1	NM_012419.5	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70998 AN: 151932 Hom.: 17229 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.467 AC: 71015 AN: 152050 Hom.: 17232 Cov.: 32 AF XY: 0.473 AC XY: 35118 AN XY: 74310

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.474

Alfa AF: 0.449 Hom.: 1945

Bravo AF: 0.466

Asia WGS AF: 0.662 AC: 2295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.1
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3968480; hg19: chr6-153432566; COSMIC: COSV52810872;