14-72603947-T-C

Variant names:

• chr14-72603947-T-C
• rs7160623
• XM_017021825.3:c.1423-26033T>C

Variant summary

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

The XM_017021825.3(RGS6):​c.1423-26033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,990 control chromosomes in the GnomAD database, including 14,332 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 0.41 (14332 hom., cov: 32)
• Consequence: RGS6 XM_017021825.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 1 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 = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	XM_017021825.3	c.1423-26033T>C		intron_variant	Intron 17 of 17		XP_016877314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62888 AN: 151872 Hom.: 14333 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.414 AC: 62902 AN: 151990 Hom.: 14332 Cov.: 32 AF XY: 0.418 AC XY: 31051 AN XY: 74252

African (AFR) AF: 0.237 AC: 9828 AN: 41456

American (AMR) AF: 0.401 AC: 6136 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2074 AN: 3472

East Asian (EAS) AF: 0.762 AC: 3931 AN: 5160

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4814

European-Finnish (FIN) AF: 0.440 AC: 4630 AN: 10522

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32425 AN: 67964

Other (OTH) AF: 0.465 AC: 980 AN: 2106

Alfa AF: 0.457 Hom.: 12743

Bravo AF: 0.404

Asia WGS AF: 0.580 AC: 2017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.75
PhyloP100		0.034

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7160623; hg19: chr14-73070655;