2-45910730-T-C

Position:

• chr2-45910730-T-C

Variant summary

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

The NM_005400.3(PRKCE):​c.413-65699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,912 control chromosomes in the GnomAD database, including 20,570 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 0.52 (20570 hom., cov: 31)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.413-65699T>C		intron_variant		ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.413-65699T>C		intron_variant		1	NM_005400.3	ENSP00000306124	P1
PRKCE	ENST00000476675.5	n.315-65699T>C		intron_variant, non_coding_transcript_variant		4
PRKCE	ENST00000480453.5	n.285-65699T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78767 AN: 151794 Hom.: 20548 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.519 AC: 78837 AN: 151912 Hom.: 20570 Cov.: 31 AF XY: 0.521 AC XY: 38652 AN XY: 74246

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.508

Alfa AF: 0.508 Hom.: 18489

Bravo AF: 0.518

Asia WGS AF: 0.567 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.47

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: rs1868389; hg19: chr2-46137869;