Genetic Variant PRKCB:c.205+15863T>C (chr16-23853269-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.296

Publications

60 publications found

Variant links:

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]

PRKCB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7 link	c.205+15863T>C	intron_variant	Intron 2 of 16	ENST00000643927.1	NP_002729.2	P05771-2
PRKCB	NM_212535.3 link	c.205+15863T>C	intron_variant	Intron 2 of 16		NP_997700.1	P05771-1
PRKCB	XM_047434365.1 link	c.-183+13310T>C	intron_variant	Intron 1 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1 link	c.205+15863T>C		intron_variant	Intron 2 of 16		NM_002738.7	ENSP00000496129.1		P05771-2

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88741

AN:

151992

Hom.:

25984

Cov.:

show subpopulations

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.:

AF XY:

0.589

AC XY:

43762

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.600

AC:

24905

AN:

41480

American (AMR)

AF:

0.531

AC:

8121

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1647

AN:

3470

East Asian (EAS)

AF:

0.606

AC:

3142

AN:

5182

South Asian (SAS)

AF:

0.618

AC:

2982

AN:

4826

European-Finnish (FIN)

AF:

0.656

AC:

6925

AN:

10558

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39129

AN:

67990

Other (OTH)

AF:

0.548

AC:

1155

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1929

3857

5786

7714

9643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.576

Hom.:

37710

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

(source)

DANN

Benign

0.75

PhyloP100

-0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over