rs1989647

Positions:

• chr16-23948099-G-A
• chr16-23948099-G-T

Variant summary

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

The NM_002738.7(PRKCB):​c.206-40409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,718 control chromosomes in the GnomAD database, including 9,809 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 0.35 (9809 hom., cov: 30)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.206-40409G>A		intron_variant		ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.206-40409G>A		intron_variant			NP_997700.1
PRKCB	XM_047434365.1	c.-182-40409G>A		intron_variant			XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.206-40409G>A		intron_variant			NM_002738.7	ENSP00000496129	A1
PRKCB	ENST00000321728.12	c.206-40409G>A		intron_variant		1		ENSP00000318315	P4
PRKCB	ENST00000498739.1	c.-27+110693G>A		intron_variant		4		ENSP00000459227

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53811 AN: 151600 Hom.: 9796 Cov.: 30

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.355 AC: 53856 AN: 151718 Hom.: 9809 Cov.: 30 AF XY: 0.357 AC XY: 26483 AN XY: 74086

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.369

Alfa AF: 0.358 Hom.: 20664

Bravo AF: 0.355

Asia WGS AF: 0.377 AC: 1312 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.47

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: rs1989647; hg19: chr16-23959420;