rs847301

Variant names:

• chr14-72234973-C-A
• rs847301
• NM_001204424.2:c.85-117122C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-72234973-C-A
• chr14-72234973-C-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.85-117122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,182 control chromosomes in the GnomAD database, including 59,467 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 0.88 (59467 hom., cov: 31)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 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.85-117122C>A		intron	N/A	NP_001191353.1
	RGS6	NM_001370275.1		c.85-117122C>A		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.85-117122C>A		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.85-117122C>A		intron	N/A	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.85-117122C>A		intron	N/A	ENSP00000451855.1
	RGS6	ENST00000404301.6	TSL:1	c.85-117122C>A		intron	N/A	ENSP00000385243.2

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133527 AN: 152064 Hom.: 59441 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.878 AC: 133602 AN: 152182 Hom.: 59467 Cov.: 31 AF XY: 0.880 AC XY: 65465 AN XY: 74410

African (AFR) AF: 0.709 AC: 29404 AN: 41464

American (AMR) AF: 0.922 AC: 14090 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3282 AN: 3466

East Asian (EAS) AF: 0.937 AC: 4853 AN: 5182

South Asian (SAS) AF: 0.939 AC: 4526 AN: 4818

European-Finnish (FIN) AF: 0.969 AC: 10290 AN: 10618

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64143 AN: 68026

Other (OTH) AF: 0.888 AC: 1878 AN: 2114

Alfa AF: 0.926 Hom.: 109241

Bravo AF: 0.868

Asia WGS AF: 0.914 AC: 3178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.36
PhyloP100		-0.32
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: rs847301; hg19: chr14-72701681;