chr14-72335528-G-A

Variant names:

• chr14-72335528-G-A
• rs2239247
• NM_001204424.2:c.85-16567G>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.85-16567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,052 control chromosomes in the GnomAD database, including 3,905 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 0.22 (3905 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.85-16567G>A		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.85-16567G>A		intron_variant	Intron 2 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33407 AN: 151934 Hom.: 3892 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.220 AC: 33472 AN: 152052 Hom.: 3905 Cov.: 32 AF XY: 0.224 AC XY: 16645 AN XY: 74334

African (AFR) AF: 0.258 AC: 10681 AN: 41464

American (AMR) AF: 0.268 AC: 4086 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2219 AN: 5152

South Asian (SAS) AF: 0.224 AC: 1081 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2092 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12225 AN: 67990

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.193 Hom.: 11914

Bravo AF: 0.223

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		-0.72
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: rs2239247; hg19: chr14-72802236;