rs2296274

Positions:

• chr14-61450460-G-A
• chr14-61450460-G-T

Variant summary

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

The NM_006255.5(PRKCH):​c.703-382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,116 control chromosomes in the GnomAD database, including 32,312 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 0.59 (32312 hom., cov: 32)
• Consequence: PRKCH NM_006255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

Genes affected

PRKCH (HGNC:9403): (protein kinase C eta) 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. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCH	NM_006255.5	c.703-382G>A		intron_variant		ENST00000332981.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCH	ENST00000332981.11	c.703-382G>A		intron_variant		1	NM_006255.5	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90470 AN: 151998 Hom.: 32316 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.595 AC: 90473 AN: 152116 Hom.: 32312 Cov.: 32 AF XY: 0.598 AC XY: 44494 AN XY: 74388

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.642

Alfa AF: 0.726 Hom.: 25180

Bravo AF: 0.581

Asia WGS AF: 0.549 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.66

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: rs2296274; hg19: chr14-61917178;