16-24104501-A-G

Variant names:

• chr16-24104501-A-G
• rs392715
• NM_002738.7:c.822-8472A>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.822-8472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,106 control chromosomes in the GnomAD database, including 36,038 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 0.69 (36038 hom., cov: 33)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 12 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]

ENSG00000307680 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.822-8472A>G		intron_variant	Intron 7 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.822-8472A>G		intron_variant	Intron 7 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.435-8472A>G		intron_variant	Intron 6 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.822-8472A>G		intron_variant	Intron 7 of 16		NM_002738.7	ENSP00000496129.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104213 AN: 151988 Hom.: 36000 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.686 AC: 104309 AN: 152106 Hom.: 36038 Cov.: 33 AF XY: 0.679 AC XY: 50507 AN XY: 74336

African (AFR) AF: 0.757 AC: 31410 AN: 41508

American (AMR) AF: 0.673 AC: 10282 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2551 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2702 AN: 5170

South Asian (SAS) AF: 0.505 AC: 2436 AN: 4820

European-Finnish (FIN) AF: 0.636 AC: 6706 AN: 10550

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45747 AN: 67996

Other (OTH) AF: 0.710 AC: 1499 AN: 2110

Alfa AF: 0.678 Hom.: 126401

Bravo AF: 0.697

Asia WGS AF: 0.563 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.69
PhyloP100		-0.56
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: rs392715; hg19: chr16-24115822;