14-72386112-A-G

Variant names:

• chr14-72386112-A-G
• rs2239219
• NM_001204424.2:c.184+33918A>G

Variant summary

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

The NM_001204424.2(RGS6):​c.184+33918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,074 control chromosomes in the GnomAD database, including 27,787 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 0.59 (27787 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 9 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]

LOC105370559 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.184+33918A>G		intron	N/A	NP_001191353.1
	RGS6	NM_001370275.1		c.184+33918A>G		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.184+33918A>G		intron	N/A	NP_001357205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.184+33918A>G		intron	N/A	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.184+33918A>G		intron	N/A	ENSP00000451855.1
	RGS6	ENST00000404301.6	TSL:1	c.184+33918A>G		intron	N/A	ENSP00000385243.2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88839 AN: 151956 Hom.: 27718 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.585 AC: 88977 AN: 152074 Hom.: 27787 Cov.: 32 AF XY: 0.587 AC XY: 43605 AN XY: 74304

African (AFR) AF: 0.807 AC: 33512 AN: 41520

American (AMR) AF: 0.542 AC: 8285 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1536 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3534 AN: 5164

South Asian (SAS) AF: 0.668 AC: 3219 AN: 4816

European-Finnish (FIN) AF: 0.520 AC: 5493 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31652 AN: 67966

Other (OTH) AF: 0.568 AC: 1197 AN: 2108

Alfa AF: 0.501 Hom.: 26035

Bravo AF: 0.590

Asia WGS AF: 0.705 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.41
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

Other links and lift over

dbSNP: rs2239219; hg19: chr14-72852820;