16-24123791-T-C

Variant names:

• chr16-24123791-T-C
• rs1013316
• NM_002738.7:c.919-44T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002738.7. 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
	PRKCB	NM_002738.7	MANE Select	c.919-44T>C		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.919-44T>C		intron	N/A	NP_997700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.919-44T>C		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.919-44T>C		intron	N/A	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

GnomAD2 exomes AF: 0.437 AC: 105602 AN: 241424 AF XY: 0.442

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 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

African (AFR) AF: 0.458 AC: 15200 AN: 33170

American (AMR) AF: 0.333 AC: 14559 AN: 43666

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11433 AN: 25458

East Asian (EAS) AF: 0.818 AC: 32395 AN: 39580

South Asian (SAS) AF: 0.513 AC: 43298 AN: 84428

European-Finnish (FIN) AF: 0.386 AC: 20437 AN: 52940

Middle Eastern (MID) AF: 0.497 AC: 2813 AN: 5660

European-Non Finnish (NFE) AF: 0.391 AC: 432162 AN: 1105442

Other (OTH) AF: 0.440 AC: 26366 AN: 59904

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

African (AFR) AF: 0.456 AC: 18897 AN: 41432

American (AMR) AF: 0.362 AC: 5530 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4135 AN: 5158

South Asian (SAS) AF: 0.526 AC: 2530 AN: 4814

European-Finnish (FIN) AF: 0.394 AC: 4165 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26411 AN: 67966

Other (OTH) AF: 0.451 AC: 951 AN: 2108

Alfa AF: 0.405 Hom.: 12795

Bravo AF: 0.425

Asia WGS AF: 0.637 AC: 2215 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	1.7
DANN	Benign	0.42
PhyloP100		0.078
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: rs1013316; hg19: chr16-24135112; COSMIC: COSV57787686;