rs11746443

chr5-177371305-G-Achr5-177371305-G-C

Variant summary

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

The NM_006480.5(RGS14):c.1337-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,770 control chromosomes in the GnomAD database, including 54,290 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 0.21 (4172 hom., cov: 30)
  • Exomes 𝑓: 0.26 (50118 hom.)
• Consequence: RGS14 NM_006480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

Genes affected

RGS14 (HGNC:9996): (regulator of G protein signaling 14) This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS14	NM_006480.5	c.1337-45G>A		intron_variant		ENST00000408923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS14	ENST00000408923.8	c.1337-45G>A		intron_variant		1	NM_006480.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32486 AN: 151912 Hom.: 4171 Cov.: 30

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.243 AC: 60643 AN: 249472 Hom.: 8054 AF XY: 0.252 AC XY: 34050 AN XY: 135362

Gnomad AFR exome AF: 0.0733

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.258 AC: 377106 AN: 1461740 Hom.: 50118 Cov.: 37 AF XY: 0.260 AC XY: 188846 AN XY: 727186

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.214 AC: 32480 AN: 152030 Hom.: 4172 Cov.: 30 AF XY: 0.216 AC XY: 16029 AN XY: 74288

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.208

Alfa AF: 0.260 Hom.: 7376

Bravo AF: 0.197

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.8
Dann	Benign	0.81

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: rs11746443; hg19: chr5-176798306; COSMIC: COSV68771153; COSMIC: COSV68771153;