rs847352

Variant names:

• chr14-72318730-G-T
• rs847352
• NM_001204424.2:c.85-33365G>T

Variant summary

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

The NM_001204424.2(RGS6):​c.85-33365G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,952 control chromosomes in the GnomAD database, including 29,396 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 0.60 (29396 hom., cov: 31)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.85-33365G>T		intron_variant	Intron 2 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.85-33365G>T		intron_variant	Intron 2 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91271 AN: 151836 Hom.: 29347 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.601 AC: 91378 AN: 151952 Hom.: 29396 Cov.: 31 AF XY: 0.604 AC XY: 44850 AN XY: 74250

African (AFR) AF: 0.842 AC: 34896 AN: 41444

American (AMR) AF: 0.569 AC: 8684 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3063 AN: 5164

South Asian (SAS) AF: 0.623 AC: 2999 AN: 4812

European-Finnish (FIN) AF: 0.533 AC: 5613 AN: 10524

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32646 AN: 67954

Other (OTH) AF: 0.569 AC: 1202 AN: 2112

Alfa AF: 0.527 Hom.: 4464

Bravo AF: 0.611

Asia WGS AF: 0.635 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.83
DANN	Benign	0.34
PhyloP100		-1.2
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: rs847352; hg19: chr14-72785438;