16-24120003-T-G

Variant names:

• chr16-24120003-T-G
• rs2283541
• NM_002738.7:c.919-3832T>G

Variant summary

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

The NM_002738.7(PRKCB):​c.919-3832T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,998 control chromosomes in the GnomAD database, including 8,727 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 0.32 (8727 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 2 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 = 0.694 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.919-3832T>G		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.919-3832T>G		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.919-3832T>G		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.919-3832T>G		intron	N/A	ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48836 AN: 151880 Hom.: 8727 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.321 AC: 48836 AN: 151998 Hom.: 8727 Cov.: 32 AF XY: 0.330 AC XY: 24540 AN XY: 74274

African (AFR) AF: 0.202 AC: 8363 AN: 41438

American (AMR) AF: 0.303 AC: 4623 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3686 AN: 5170

South Asian (SAS) AF: 0.481 AC: 2317 AN: 4820

European-Finnish (FIN) AF: 0.413 AC: 4354 AN: 10552

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23159 AN: 67962

Other (OTH) AF: 0.345 AC: 728 AN: 2108

Alfa AF: 0.320 Hom.: 1058

Bravo AF: 0.308

Asia WGS AF: 0.553 AC: 1922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.69
PhyloP100		-0.13
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: rs2283541; hg19: chr16-24131324;