chr2-46084821-A-C

Variant names:

• chr2-46084821-A-C
• rs13432276
• NM_005400.3:c.1438-1387A>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.1438-1387A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,300 control chromosomes in the GnomAD database, including 13,130 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 0.41 (13130 hom., cov: 29)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005400.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	NM_005400.3	MANE Select	c.1438-1387A>C		intron	N/A	NP_005391.1	Q02156

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCE	ENST00000306156.8	TSL:1 MANE Select	c.1438-1387A>C		intron	N/A	ENSP00000306124.3	Q02156
	PRKCE	ENST00000872579.1		c.1027-1387A>C		intron	N/A	ENSP00000542638.1
	PRKCE	ENST00000469753.5	TSL:3	n.525-1387A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 61943 AN: 151198 Hom.: 13115 Cov.: 29

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.410 AC: 61997 AN: 151300 Hom.: 13130 Cov.: 29 AF XY: 0.412 AC XY: 30446 AN XY: 73838

African (AFR) AF: 0.504 AC: 20761 AN: 41168

American (AMR) AF: 0.397 AC: 6032 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2663 AN: 5148

South Asian (SAS) AF: 0.483 AC: 2312 AN: 4784

European-Finnish (FIN) AF: 0.320 AC: 3308 AN: 10350

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23907 AN: 67874

Other (OTH) AF: 0.426 AC: 893 AN: 2098

Alfa AF: 0.381 Hom.: 8807

Bravo AF: 0.418

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.16
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: rs13432276; hg19: chr2-46311960;