2-45706812-G-T

Variant names:

• chr2-45706812-G-T
• rs10495926
• NM_005400.3:c.348+54364G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005400.3(PRKCE):​c.348+54364G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,268 control chromosomes in the GnomAD database, including 254 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 0.040 (254 hom., cov: 33)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.348+54364G>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+54364G>T		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6020 AN: 152150 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0395 AC: 6015 AN: 152268 Hom.: 254 Cov.: 33 AF XY: 0.0407 AC XY: 3027 AN XY: 74440

African (AFR) AF: 0.0805 AC: 3344 AN: 41520

American (AMR) AF: 0.0857 AC: 1311 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.150 AC: 776 AN: 5188

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4824

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00513 AC: 349 AN: 68032

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0308 Hom.: 88

Bravo AF: 0.0499

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10495926; hg19: chr2-45933951;