rs2239266

Variant names:

• chr14-72010015-G-A
• rs2239266
• NM_001204424.2:c.84+45140G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204424.2(RGS6):​c.84+45140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,238 control chromosomes in the GnomAD database, including 992 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 0.075 (992 hom., cov: 33)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204424.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.84+45140G>A		intron	N/A	NP_001191353.1	P49758-3
	RGS6	NM_001370275.1		c.84+45140G>A		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.84+45140G>A		intron	N/A	NP_001357205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.84+45140G>A		intron	N/A	ENSP00000451030.1	P49758-3
	RGS6	ENST00000556437.5	TSL:1	c.84+45140G>A		intron	N/A	ENSP00000451855.1	P49758-3
	RGS6	ENST00000404301.6	TSL:1	c.84+45140G>A		intron	N/A	ENSP00000385243.2	P49758-15

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11411 AN: 152120 Hom.: 993 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00878

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0751 AC: 11428 AN: 152238 Hom.: 992 Cov.: 33 AF XY: 0.0773 AC XY: 5754 AN XY: 74444

African (AFR) AF: 0.183 AC: 7618 AN: 41520

American (AMR) AF: 0.0766 AC: 1172 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5166

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4826

European-Finnish (FIN) AF: 0.0412 AC: 438 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00878 AC: 597 AN: 68018

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0328 Hom.: 1241

Bravo AF: 0.0834

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2239266;

hg19: chr14-72476732;