rs10149848

Variant names:

• chr14-72388454-G-A
• rs10149848
• NM_001204424.2:c.184+36260G>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.184+36260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,134 control chromosomes in the GnomAD database, including 1,619 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 0.13 (1619 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 6 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]

LOC105370559 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.184+36260G>A		intron_variant	Intron 3 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.184+36260G>A		intron_variant	Intron 3 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19378 AN: 152016 Hom.: 1612 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.128 AC: 19420 AN: 152134 Hom.: 1619 Cov.: 32 AF XY: 0.126 AC XY: 9342 AN XY: 74376

African (AFR) AF: 0.234 AC: 9714 AN: 41478

American (AMR) AF: 0.130 AC: 1989 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3468

East Asian (EAS) AF: 0.00887 AC: 46 AN: 5188

South Asian (SAS) AF: 0.0959 AC: 463 AN: 4826

European-Finnish (FIN) AF: 0.0723 AC: 765 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5774 AN: 67988

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.0957 Hom.: 2217

Bravo AF: 0.135

Asia WGS AF: 0.0710 AC: 247 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	1.5
DANN	Benign	0.63
PhyloP100		-0.35
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: rs10149848; hg19: chr14-72855162;