16-23898631-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+61225T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,120 control chromosomes in the GnomAD database, including 46,997 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 0.78 (46997 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCB	NM_002738.7	c.205+61225T>G		intron_variant		ENST00000643927.1
PRKCB	NM_212535.3	c.205+61225T>G		intron_variant
PRKCB	XM_047434365.1	c.-183+58672T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCB	ENST00000643927.1	c.205+61225T>G		intron_variant			NM_002738.7	A1
PRKCB	ENST00000321728.12	c.205+61225T>G		intron_variant		1		P4
PRKCB	ENST00000498739.1	c.-27+61225T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118569 AN: 152002 Hom.: 46983 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.780 AC: 118628 AN: 152120 Hom.: 46997 Cov.: 31 AF XY: 0.784 AC XY: 58302 AN XY: 74372

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.786

Alfa AF: 0.818 Hom.: 67797

Bravo AF: 0.776

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	12
Dann	Benign	0.75

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: rs9922316; hg19: chr16-23909952;