rs7404095

chr16-23853269-T-Cchr16-23853269-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002738.7(PRKCB):c.205+15863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,110 control chromosomes in the GnomAD database, including 25,993 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 0.58 (25993 hom., cov: 33)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCB	NM_002738.7	c.205+15863T>C		intron_variant		ENST00000643927.1
PRKCB	NM_212535.3	c.205+15863T>C		intron_variant
PRKCB	XM_047434365.1	c.-183+13310T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCB	ENST00000643927.1	c.205+15863T>C		intron_variant			NM_002738.7	A1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88741 AN: 151992 Hom.: 25984 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.584 AC: 88781 AN: 152110 Hom.: 25993 Cov.: 33 AF XY: 0.589 AC XY: 43762 AN XY: 74352

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.548

Alfa AF: 0.555 Hom.: 3882

Bravo AF: 0.567

Asia WGS AF: 0.610 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.8
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs7404095; hg19: chr16-23864590;