14-61428327-T-C

Variant names:

• chr14-61428327-T-C
• rs11158345
• NM_006255.5:c.428-14784T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000332981.11(PRKCH):​c.428-14784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,888 control chromosomes in the GnomAD database, including 3,777 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 0.21 (3777 hom., cov: 30)
• Consequence: PRKCH ENST00000332981.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332981.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	NM_006255.5	MANE Select	c.428-14784T>C		intron	N/A	NP_006246.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.428-14784T>C		intron	N/A	ENSP00000329127.5
	PRKCH	ENST00000555082.6	TSL:1	c.-56-14784T>C		intron	N/A	ENSP00000450981.1
	PRKCH	ENST00000557585.5	TSL:5	c.-56-14784T>C		intron	N/A	ENSP00000451930.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32174 AN: 151768 Hom.: 3771 Cov.: 30

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.212 AC: 32203 AN: 151888 Hom.: 3777 Cov.: 30 AF XY: 0.215 AC XY: 15990 AN XY: 74232

African (AFR) AF: 0.166 AC: 6873 AN: 41384

American (AMR) AF: 0.361 AC: 5514 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3468

East Asian (EAS) AF: 0.272 AC: 1402 AN: 5158

South Asian (SAS) AF: 0.205 AC: 986 AN: 4810

European-Finnish (FIN) AF: 0.176 AC: 1855 AN: 10550

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13733 AN: 67948

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.211 Hom.: 1013

Bravo AF: 0.225

Asia WGS AF: 0.240 AC: 837 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	6.7
DANN	Benign	0.76
PhyloP100		0.31
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: rs11158345; hg19: chr14-61895045;