14-72361020-C-T

Variant names:

• chr14-72361020-C-T
• rs847334
• NM_001204424.2:c.184+8826C>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.184+8826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,356 control chromosomes in the GnomAD database, including 13,485 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 0.38 (13485 hom., cov: 29)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.184+8826C>T		intron	N/A	NP_001191353.1	P49758-3
	RGS6	NM_001370275.1		c.184+8826C>T		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.184+8826C>T		intron	N/A	NP_001357205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.184+8826C>T		intron	N/A	ENSP00000451030.1	P49758-3
	RGS6	ENST00000556437.5	TSL:1	c.184+8826C>T		intron	N/A	ENSP00000451855.1	P49758-3
	RGS6	ENST00000404301.6	TSL:1	c.184+8826C>T		intron	N/A	ENSP00000385243.2	P49758-15

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58116 AN: 151252 Hom.: 13462 Cov.: 29

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.384 AC: 58185 AN: 151356 Hom.: 13485 Cov.: 29 AF XY: 0.383 AC XY: 28292 AN XY: 73874

African (AFR) AF: 0.657 AC: 27120 AN: 41304

American (AMR) AF: 0.284 AC: 4326 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1037 AN: 3462

East Asian (EAS) AF: 0.0994 AC: 507 AN: 5100

South Asian (SAS) AF: 0.430 AC: 2058 AN: 4786

European-Finnish (FIN) AF: 0.314 AC: 3230 AN: 10294

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.276 AC: 18733 AN: 67894

Other (OTH) AF: 0.367 AC: 771 AN: 2098

Alfa AF: 0.307 Hom.: 30262

Bravo AF: 0.391

Asia WGS AF: 0.326 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.57
PhyloP100		-0.79
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: rs847334; hg19: chr14-72827728;