2-45797073-T-C

Variant names:

• chr2-45797073-T-C
• rs6720975
• NM_005400.3:c.349-45927T>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.349-45927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,118 control chromosomes in the GnomAD database, including 37,204 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 0.68 (37204 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.349-45927T>C		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.349-45927T>C		intron_variant	Intron 1 of 14	1	NM_005400.3	ENSP00000306124.3

Frequencies

GnomAD3 genomes AF: 0.684 AC: 104000 AN: 152000 Hom.: 37157 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.684 AC: 104105 AN: 152118 Hom.: 37204 Cov.: 32 AF XY: 0.683 AC XY: 50805 AN XY: 74340

African (AFR) AF: 0.897 AC: 37249 AN: 41518

American (AMR) AF: 0.694 AC: 10616 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2243 AN: 3466

East Asian (EAS) AF: 0.726 AC: 3761 AN: 5184

South Asian (SAS) AF: 0.759 AC: 3657 AN: 4820

European-Finnish (FIN) AF: 0.569 AC: 5998 AN: 10546

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38453 AN: 67968

Other (OTH) AF: 0.684 AC: 1444 AN: 2112

Alfa AF: 0.607 Hom.: 120387

Bravo AF: 0.703

Asia WGS AF: 0.760 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.5
DANN	Benign	0.63
PhyloP100		0.78
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: rs6720975; hg19: chr2-46024212;