rs12892244

Positions:

• chr14-72355005-C-A
• chr14-72355005-C-T

Variant summary

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

The NM_001204424.2(RGS6):​c.184+2811C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,920 control chromosomes in the GnomAD database, including 2,837 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 0.18 (2837 hom., cov: 31)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.184+2811C>A		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.184+2811C>A		intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27485 AN: 151802 Hom.: 2828 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.181 AC: 27536 AN: 151920 Hom.: 2837 Cov.: 31 AF XY: 0.187 AC XY: 13877 AN XY: 74254

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.169

Alfa AF: 0.164 Hom.: 1724

Bravo AF: 0.180

Asia WGS AF: 0.309 AC: 1073 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.36

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: rs12892244; hg19: chr14-72821713;