rs2239223

chr14-72382801-C-Achr14-72382801-C-Gchr14-72382801-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS6	NM_001204424.2	c.184+30607C>A		intron_variant		ENST00000553525.6
LOC105370559	XR_944018.3	n.335-100G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.184+30607C>A		intron_variant		2	NM_001204424.2	P1

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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.529

Alfa AF: 0.452 Hom.: 18804

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

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: rs2239223; hg19: chr14-72849509;