rs4953318

Variant names:

• chr2-46127912-A-C
• rs4953318
• NM_005400.3:c.1593-17181A>C

Variant summary

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

The NM_005400.3(PRKCE):​c.1593-17181A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,102 control chromosomes in the GnomAD database, including 14,835 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 0.42 (14835 hom., cov: 33)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1593-17181A>C		intron_variant	Intron 11 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1593-17181A>C		intron_variant	Intron 11 of 14	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000469753.5	n.680-17181A>C		intron_variant	Intron 2 of 3	3
PRKCE	ENST00000480633.1	n.359-17181A>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64399 AN: 151982 Hom.: 14816 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.424 AC: 64462 AN: 152102 Hom.: 14835 Cov.: 33 AF XY: 0.418 AC XY: 31050 AN XY: 74346

African (AFR) AF: 0.598 AC: 24821 AN: 41484

American (AMR) AF: 0.329 AC: 5031 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1130 AN: 5178

South Asian (SAS) AF: 0.372 AC: 1791 AN: 4814

European-Finnish (FIN) AF: 0.301 AC: 3181 AN: 10576

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25702 AN: 67980

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.394 Hom.: 33816

Bravo AF: 0.428

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		0.018
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: rs4953318; hg19: chr2-46355051;