rs10131300

chr14-72472787-C-Achr14-72472787-C-Gchr14-72472787-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001204424.2(RGS6):c.537-85C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 979,808 control chromosomes in the GnomAD database, including 246,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38324 hom., cov: 32)
  • Exomes 𝑓: 0.71 (208651 hom.)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.144

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-72472787-C-A is Benign according to our data. Variant chr14-72472787-C-A is described in ClinVar as [Benign]. Clinvar id is 1243968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.537-85C>A		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.537-85C>A		intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107417 AN: 151968 Hom.: 38295 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.702

GnomAD4 exome AF: 0.706 AC: 584278 AN: 827722 Hom.: 208651 AF XY: 0.707 AC XY: 305872 AN XY: 432922

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.984

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.711

GnomAD4 genome AF: 0.707 AC: 107495 AN: 152086 Hom.: 38324 Cov.: 32 AF XY: 0.713 AC XY: 53009 AN XY: 74346

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.705

Alfa AF: 0.679 Hom.: 69025

Bravo AF: 0.716

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.2
Dann	Benign	0.53

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: rs10131300; hg19: chr14-72939495;