2-45726771-C-T

Variant names:

• chr2-45726771-C-T
• rs1464572
• NM_005400.3:c.348+74323C>T

Variant summary

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

The NM_005400.3(PRKCE):​c.348+74323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,928 control chromosomes in the GnomAD database, including 10,433 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 0.37 (10433 hom., cov: 31)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.348+74323C>T		intron_variant	Intron 1 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.348+74323C>T		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55948 AN: 151808 Hom.: 10438 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.368 AC: 55960 AN: 151928 Hom.: 10433 Cov.: 31 AF XY: 0.372 AC XY: 27599 AN XY: 74230

African (AFR) AF: 0.325 AC: 13477 AN: 41428

American (AMR) AF: 0.350 AC: 5332 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1981 AN: 5176

South Asian (SAS) AF: 0.496 AC: 2392 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4416 AN: 10538

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25940 AN: 67934

Other (OTH) AF: 0.337 AC: 712 AN: 2110

Alfa AF: 0.372 Hom.: 25409

Bravo AF: 0.354

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.50
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1464572; hg19: chr2-45953910;