chr14-72269330-G-A

Variant names:

• chr14-72269330-G-A
• rs847342
• NM_001204424.2:c.85-82765G>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.85-82765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,136 control chromosomes in the GnomAD database, including 50,435 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 0.81 (50435 hom., cov: 32)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.85-82765G>A		intron	N/A	NP_001191353.1
	RGS6	NM_001370275.1		c.85-82765G>A		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.85-82765G>A		intron	N/A	NP_001357205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.85-82765G>A		intron	N/A	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.85-82765G>A		intron	N/A	ENSP00000451855.1
	RGS6	ENST00000404301.6	TSL:1	c.85-82765G>A		intron	N/A	ENSP00000385243.2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123290 AN: 152018 Hom.: 50410 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.811 AC: 123364 AN: 152136 Hom.: 50435 Cov.: 32 AF XY: 0.812 AC XY: 60360 AN XY: 74352

African (AFR) AF: 0.699 AC: 28989 AN: 41492

American (AMR) AF: 0.795 AC: 12145 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3032 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4075 AN: 5148

South Asian (SAS) AF: 0.826 AC: 3986 AN: 4828

European-Finnish (FIN) AF: 0.894 AC: 9468 AN: 10588

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58844 AN: 68004

Other (OTH) AF: 0.813 AC: 1718 AN: 2114

Alfa AF: 0.847 Hom.: 246073

Bravo AF: 0.802

Asia WGS AF: 0.809 AC: 2813 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	1.5
DANN	Benign	0.78
PhyloP100		-0.59
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: rs847342; hg19: chr14-72736038;