chr6-153032723-T-C

Position:

• chr6-153032723-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.120-6180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,004 control chromosomes in the GnomAD database, including 21,004 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 0.52 (21004 hom., cov: 32)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS17	NM_012419.5	c.120-6180A>G		intron_variant		ENST00000206262.2
RGS17	XM_047418634.1	c.165-6180A>G		intron_variant
RGS17	XM_047418635.1	c.153-6180A>G		intron_variant
RGS17	XM_047418636.1	c.120-6180A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS17	ENST00000206262.2	c.120-6180A>G		intron_variant		1	NM_012419.5	P1
RGS17	ENST00000367225.6	c.120-6180A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79133 AN: 151886 Hom.: 20975 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.521 AC: 79217 AN: 152004 Hom.: 21004 Cov.: 32 AF XY: 0.524 AC XY: 38946 AN XY: 74292

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.512

Alfa AF: 0.498 Hom.: 3827

Bravo AF: 0.533

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.64

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: rs516557; hg19: chr6-153353858;