14-61450460-G-A

Variant names:

• chr14-61450460-G-A
• rs2296274
• NM_006255.5:c.703-382G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006255.5. 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
	PRKCH	NM_006255.5	MANE Select	c.703-382G>A		intron	N/A	NP_006246.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCH	ENST00000332981.11	TSL:1 MANE Select	c.703-382G>A		intron	N/A	ENSP00000329127.5	P24723-1
	PRKCH	ENST00000555082.6	TSL:1	c.220-382G>A		intron	N/A	ENSP00000450981.1	P24723-2
	PRKCH	ENST00000557585.5	TSL:5	c.220-382G>A		intron	N/A	ENSP00000451930.1	G3V4Q6

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

African (AFR) AF: 0.178 AC: 7365 AN: 41476

American (AMR) AF: 0.771 AC: 11775 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2579 AN: 5172

South Asian (SAS) AF: 0.595 AC: 2866 AN: 4816

European-Finnish (FIN) AF: 0.778 AC: 8232 AN: 10586

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52681 AN: 68004

Other (OTH) AF: 0.642 AC: 1355 AN: 2112

Alfa AF: 0.702 Hom.: 85084

Bravo AF: 0.581

Asia WGS AF: 0.549 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.66
PhyloP100		1.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2296274; hg19: chr14-61917178;