rs4903031

Variant names:

• chr14-72552528-A-G
• rs4903031
• NM_001204424.2:c.1423-9889A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204424.2(RGS6):​c.1423-9889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,224 control chromosomes in the GnomAD database, including 2,986 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 0.19 (2985 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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]

ENSG00000258871 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.1423-9889A>G		intron_variant	Intron 17 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.1423-9889A>G		intron_variant	Intron 17 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29051 AN: 152058 Hom.: 2990 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.125 AC: 6 AN: 48 Hom.: 1 AF XY: 0.156 AC XY: 5 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.191 AC: 29052 AN: 152176 Hom.: 2985 Cov.: 32 AF XY: 0.191 AC XY: 14205 AN XY: 74398

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.214

Alfa AF: 0.216 Hom.: 8250

Bravo AF: 0.190

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69

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: rs4903031; hg19: chr14-73019236;