rs2239227

Positions:

• chr14-72363271-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.184+11077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,286 control chromosomes in the GnomAD database, including 1,082 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 0.12 (1082 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.184+11077A>G		intron_variant		ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.184+11077A>G		intron_variant		2	NM_001204424.2	ENSP00000451030	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18046 AN: 152168 Hom.: 1080 Cov.: 32

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.119 AC: 18073 AN: 152286 Hom.: 1082 Cov.: 32 AF XY: 0.123 AC XY: 9163 AN XY: 74476

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.100

Alfa AF: 0.126 Hom.: 612

Bravo AF: 0.115

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.60

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: rs2239227; hg19: chr14-72829979;