rs8007684

Variant names:

• chr14-72347856-G-T
• rs8007684
• NM_001204424.2:c.85-4239G>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.85-4239G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,198 control chromosomes in the GnomAD database, including 1,525 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 0.14 (1525 hom., cov: 33)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866
• 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 (EAS) allele frequency at 95% confidence interval = 0.17 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.85-4239G>T		intron	N/A	NP_001191353.1	P49758-3
	RGS6	NM_001370275.1		c.85-4239G>T		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.85-4239G>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.85-4239G>T		intron	N/A	ENSP00000451030.1	P49758-3
	RGS6	ENST00000556437.5	TSL:1	c.85-4239G>T		intron	N/A	ENSP00000451855.1	P49758-3
	RGS6	ENST00000404301.6	TSL:1	c.85-4239G>T		intron	N/A	ENSP00000385243.2	P49758-15

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21855 AN: 152080 Hom.: 1520 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.144 AC: 21891 AN: 152198 Hom.: 1525 Cov.: 33 AF XY: 0.147 AC XY: 10957 AN XY: 74412

African (AFR) AF: 0.140 AC: 5813 AN: 41528

American (AMR) AF: 0.165 AC: 2521 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.180 AC: 932 AN: 5182

South Asian (SAS) AF: 0.167 AC: 804 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9510 AN: 68016

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.138 Hom.: 6220

Bravo AF: 0.142

Asia WGS AF: 0.177 AC: 616 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	1.3
DANN	Benign	0.68
PhyloP100		-0.87
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: rs8007684; hg19: chr14-72814564;