rs999499

Variant names:

• chr16-24142342-G-A
• rs999499
• NM_002738.7:c.1066-12342G>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.1066-12342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 152,312 control chromosomes in the GnomAD database, including 361 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 0.037 (361 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	NM_002738.7	MANE Select	c.1066-12342G>A		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.1066-12342G>A		intron	N/A	NP_997700.1	P05771-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.1066-12342G>A		intron	N/A	ENSP00000496129.1	P05771-2
	PRKCB	ENST00000321728.12	TSL:1	c.1066-12342G>A		intron	N/A	ENSP00000318315.7	P05771-1
	PRKCB	ENST00000965655.1		c.1144-12342G>A		intron	N/A	ENSP00000635714.1

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5657 AN: 152194 Hom.: 362 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0372 AC: 5662 AN: 152312 Hom.: 361 Cov.: 32 AF XY: 0.0366 AC XY: 2724 AN XY: 74490

African (AFR) AF: 0.127 AC: 5291 AN: 41548

American (AMR) AF: 0.0174 AC: 267 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68026

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0322 Hom.: 39

Bravo AF: 0.0418

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		0.10
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: rs999499; hg19: chr16-24153663;