chr14-72382801-C-A

Variant names:

• chr14-72382801-C-A
• rs2239223
• NM_001204424.2:c.184+30607C>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.184+30607C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,984 control chromosomes in the GnomAD database, including 25,570 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 0.56 (25570 hom., cov: 31)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 8 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.184+30607C>A		intron_variant	Intron 3 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.184+30607C>A		intron_variant	Intron 3 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84733 AN: 151866 Hom.: 25507 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.558 AC: 84868 AN: 151984 Hom.: 25570 Cov.: 31 AF XY: 0.562 AC XY: 41719 AN XY: 74288

African (AFR) AF: 0.787 AC: 32647 AN: 41488

American (AMR) AF: 0.515 AC: 7857 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1489 AN: 3468

East Asian (EAS) AF: 0.679 AC: 3504 AN: 5164

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4814

European-Finnish (FIN) AF: 0.508 AC: 5360 AN: 10546

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29263 AN: 67918

Other (OTH) AF: 0.529 AC: 1117 AN: 2110

Alfa AF: 0.475 Hom.: 39130

Bravo AF: 0.563

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.27
PhyloP100		-2.1
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: rs2239223; hg19: chr14-72849509;