16-24050128-T-C

Variant names:

• chr16-24050128-T-C
• rs1976194
• NM_002738.7:c.529+14581T>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.529+14581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,988 control chromosomes in the GnomAD database, including 22,130 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 0.52 (22130 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 13 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.529+14581T>C		intron_variant	Intron 5 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.529+14581T>C		intron_variant	Intron 5 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.142+14581T>C		intron_variant	Intron 4 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.529+14581T>C		intron_variant	Intron 5 of 16		NM_002738.7	ENSP00000496129.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79551 AN: 151870 Hom.: 22087 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.524 AC: 79648 AN: 151988 Hom.: 22130 Cov.: 31 AF XY: 0.517 AC XY: 38363 AN XY: 74274

African (AFR) AF: 0.704 AC: 29184 AN: 41452

American (AMR) AF: 0.426 AC: 6515 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3466

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5168

South Asian (SAS) AF: 0.395 AC: 1905 AN: 4828

European-Finnish (FIN) AF: 0.431 AC: 4542 AN: 10540

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32000 AN: 67946

Other (OTH) AF: 0.544 AC: 1145 AN: 2106

Alfa AF: 0.488 Hom.: 58002

Bravo AF: 0.534

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.086
DANN	Benign	0.57
PhyloP100		-1.6
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: rs1976194; hg19: chr16-24061449;