14-72312321-G-T

Position:

• chr14-72312321-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204424.2(RGS6):​c.85-39774G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 149,380 control chromosomes in the GnomAD database, including 1,794 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 0.13 (1794 hom., cov: 31)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.85-39774G>T		intron_variant		ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.85-39774G>T		intron_variant		2	NM_001204424.2	ENSP00000451030	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18683 AN: 149264 Hom.: 1791 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0915

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.125 AC: 18724 AN: 149380 Hom.: 1794 Cov.: 31 AF XY: 0.123 AC XY: 8930 AN XY: 72624

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0920 Hom.: 179

Bravo AF: 0.134

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.63
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2283394; hg19: chr14-72779029;