rs2239250

Positions:

• chr14-72318972-A-G

Variant summary

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

The NM_001204424.2(RGS6):​c.85-33123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,124 control chromosomes in the GnomAD database, including 2,031 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 0.16 (2031 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.85-33123A>G		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.85-33123A>G		intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24865 AN: 152006 Hom.: 2025 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.164 AC: 24896 AN: 152124 Hom.: 2031 Cov.: 32 AF XY: 0.167 AC XY: 12447 AN XY: 74368

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.137

Alfa AF: 0.147 Hom.: 859

Bravo AF: 0.164

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2239250; hg19: chr14-72785680;