16-24123791-T-C

Position:

• chr16-24123791-T-C

Variant summary

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

The NM_002738.7(PRKCB):​c.919-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,602,228 control chromosomes in the GnomAD database, including 142,822 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 0.43 (14278 hom., cov: 31)
  • Exomes 𝑓: 0.41 (128544 hom.)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.919-44T>C		intron_variant		ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.919-44T>C		intron_variant			NP_997700.1
PRKCB	XM_047434365.1	c.532-44T>C		intron_variant			XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.919-44T>C		intron_variant			NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.919-44T>C		intron_variant		1		ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64636 AN: 151862 Hom.: 14269 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.437 AC: 105602 AN: 241424 Hom.: 24689 AF XY: 0.442 AC XY: 57642 AN XY: 130320

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.803

Gnomad SAS exome AF: 0.513

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.413 AC: 598663 AN: 1450248 Hom.: 128544 Cov.: 31 AF XY: 0.416 AC XY: 299760 AN XY: 720672

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.426 AC: 64671 AN: 151980 Hom.: 14278 Cov.: 31 AF XY: 0.430 AC XY: 31926 AN XY: 74262

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.451

Alfa AF: 0.406 Hom.: 9640

Bravo AF: 0.425

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.42

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: rs1013316; hg19: chr16-24135112; COSMIC: COSV57787686;