rs429342

chr16-24155127-G-C

Variant summary

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

The NM_002738.7(PRKCB):c.1239+270G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,172 control chromosomes in the GnomAD database, including 4,271 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 0.23 (4271 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556

Genes affected

PRKCB (HGNC:9395): (protein kinase C beta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and 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 protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCB	NM_002738.7	c.1239+270G>C		intron_variant		ENST00000643927.1
PRKCB	NM_212535.3	c.1239+270G>C		intron_variant
PRKCB	XM_047434365.1	c.852+270G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCB	ENST00000643927.1	c.1239+270G>C		intron_variant			NM_002738.7	A1
PRKCB	ENST00000321728.12	c.1239+270G>C		intron_variant		1		P4
PRKCB	ENST00000472066.1	c.180+270G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35074 AN: 152054 Hom.: 4268 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.231 AC: 35094 AN: 152172 Hom.: 4271 Cov.: 32 AF XY: 0.229 AC XY: 17010 AN XY: 74410

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.238

Alfa AF: 0.227 Hom.: 492

Bravo AF: 0.230

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.1
Dann	Benign	0.78

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: rs429342; hg19: chr16-24166448;