rs867286

Variant names:

• chr2-45754891-G-A
• rs867286
• NM_005400.3:c.349-88109G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-45754891-G-A
• chr2-45754891-G-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.349-88109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,160 control chromosomes in the GnomAD database, including 6,929 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 0.29 (6929 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 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.349-88109G>A		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.349-88109G>A		intron	N/A	ENSP00000306124.3	Q02156
	PRKCE	ENST00000467135.5	TSL:1	n.400+53400G>A		intron	N/A
	PRKCE	ENST00000872579.1		c.349-88109G>A		intron	N/A	ENSP00000542638.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44749 AN: 152040 Hom.: 6930 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.294 AC: 44766 AN: 152160 Hom.: 6929 Cov.: 32 AF XY: 0.297 AC XY: 22120 AN XY: 74374

African (AFR) AF: 0.201 AC: 8359 AN: 41522

American (AMR) AF: 0.326 AC: 4984 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2024 AN: 5168

South Asian (SAS) AF: 0.333 AC: 1608 AN: 4828

European-Finnish (FIN) AF: 0.366 AC: 3867 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22132 AN: 67998

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.311 Hom.: 29379

Bravo AF: 0.288

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.71
PhyloP100		0.14
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: rs867286; hg19: chr2-45982030;