rs884399

Positions:

• chr2-45755786-G-T

Variant summary

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

The NM_005400.3(PRKCE):​c.349-87214G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,070 control chromosomes in the GnomAD database, including 6,613 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 0.28 (6613 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

Genes affected

PRKCE (HGNC:9401): (protein kinase C epsilon) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-87214G>T		intron_variant		ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.349-87214G>T		intron_variant		1	NM_005400.3	ENSP00000306124	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43030 AN: 151952 Hom.: 6618 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.283 AC: 43027 AN: 152070 Hom.: 6613 Cov.: 32 AF XY: 0.287 AC XY: 21311 AN XY: 74328

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.268

Alfa AF: 0.312 Hom.: 4582

Bravo AF: 0.275

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
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: rs884399; hg19: chr2-45982925;