rs4902960

Variant names:

• chr14-71965432-G-A
• rs4902960
• NM_001204424.2:c.84+557G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370275.1(RGS6):​c.84+557G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,248 control chromosomes in the GnomAD database, including 518 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 0.074 (518 hom., cov: 33)
• Consequence: RGS6 NM_001370275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370275.1. 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.84+557G>A		intron	N/A	NP_001191353.1
	RGS6	NM_001370275.1		c.84+557G>A		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.84+557G>A		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.84+557G>A		intron	N/A	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.84+557G>A		intron	N/A	ENSP00000451855.1
	RGS6	ENST00000404301.6	TSL:1	c.84+557G>A		intron	N/A	ENSP00000385243.2

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11225 AN: 152130 Hom.: 520 Cov.: 33

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0737 AC: 11227 AN: 152248 Hom.: 518 Cov.: 33 AF XY: 0.0746 AC XY: 5554 AN XY: 74444

African (AFR) AF: 0.0924 AC: 3837 AN: 41542

American (AMR) AF: 0.0807 AC: 1234 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1071 AN: 5182

South Asian (SAS) AF: 0.0768 AC: 370 AN: 4816

European-Finnish (FIN) AF: 0.0757 AC: 803 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3438 AN: 68024

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0599 Hom.: 1394

Bravo AF: 0.0774

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.57
PhyloP100		-0.12
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: rs4902960; hg19: chr14-72432149;