NM_002738.7:c.289-13683C>A

Variant names:

• chr16-24018453-C-A
• rs8054767
• NM_002738.7:c.289-13683C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002738.7(PRKCB):​c.289-13683C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,102 control chromosomes in the GnomAD database, including 3,042 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 0.20 (3042 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.289-13683C>A		intron_variant	Intron 3 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.289-13683C>A		intron_variant	Intron 3 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-99-13683C>A		intron_variant	Intron 2 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.289-13683C>A		intron_variant	Intron 3 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.289-13683C>A		intron_variant	Intron 3 of 16	1		ENSP00000318315.7
PRKCB	ENST00000498739.1	c.-26-74338C>A		intron_variant	Intron 1 of 3	4		ENSP00000459227.1
PRKCB	ENST00000647422.1	n.189-13683C>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30050 AN: 151982 Hom.: 3035 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.198 AC: 30093 AN: 152102 Hom.: 3042 Cov.: 32 AF XY: 0.200 AC XY: 14870 AN XY: 74362

African (AFR) AF: 0.213 AC: 8832 AN: 41488

American (AMR) AF: 0.147 AC: 2250 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1587 AN: 5172

South Asian (SAS) AF: 0.150 AC: 725 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2483 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12772 AN: 67990

Other (OTH) AF: 0.197 AC: 415 AN: 2110

Alfa AF: 0.190 Hom.: 12189

Bravo AF: 0.193

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		0.79
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: rs8054767; hg19: chr16-24029774;