6-153020649-T-C

Position:

• chr6-153020649-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+3613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,976 control chromosomes in the GnomAD database, including 9,768 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 0.36 (9768 hom., cov: 31)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.444+3613A>G		intron_variant		ENST00000206262.2
RGS17	XM_047418634.1	c.489+3613A>G		intron_variant
RGS17	XM_047418635.1	c.477+3613A>G		intron_variant
RGS17	XM_047418636.1	c.444+3613A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.444+3613A>G		intron_variant		1	NM_012419.5	P1
RGS17	ENST00000367225.6	c.444+3613A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54029 AN: 151858 Hom.: 9754 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.356 AC: 54091 AN: 151976 Hom.: 9768 Cov.: 31 AF XY: 0.357 AC XY: 26507 AN XY: 74264

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.321

Alfa AF: 0.334 Hom.: 1083

Bravo AF: 0.354

Asia WGS AF: 0.368 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
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: rs610614; hg19: chr6-153341784;