16-24127248-T-C

Position:

• chr16-24127248-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.1065+3267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,300 control chromosomes in the GnomAD database, including 17,650 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 0.48 (17650 hom., cov: 30)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.1065+3267T>C		intron_variant		ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.1065+3267T>C		intron_variant			NP_997700.1
PRKCB	XM_047434365.1	c.678+3267T>C		intron_variant			XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.1065+3267T>C		intron_variant			NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.1065+3267T>C		intron_variant		1		ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72326 AN: 151178 Hom.: 17616 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.479 AC: 72411 AN: 151300 Hom.: 17650 Cov.: 30 AF XY: 0.478 AC XY: 35307 AN XY: 73896

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.474

Alfa AF: 0.457 Hom.: 1947

Bravo AF: 0.481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.43

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: rs198193; hg19: chr16-24138569;