dbSNP rs198185: PRKCB:c.919-774A>T (chr16-24123061-A-T) – 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.919-774A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,262 control chromosomes in the GnomAD database, including 1,933 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 0.14 ( 1933 hom., cov: 33)

Consequence

PRKCB
NM_002738.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

6 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7 link	c.919-774A>T	intron_variant	Intron 8 of 16	ENST00000643927.1	NP_002729.2	P05771-2
PRKCB	NM_212535.3 link	c.919-774A>T	intron_variant	Intron 8 of 16		NP_997700.1	P05771-1
PRKCB	XM_047434365.1 link	c.532-774A>T	intron_variant	Intron 7 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1 link	c.919-774A>T		intron_variant	Intron 8 of 16		NM_002738.7	ENSP00000496129.1		P05771-2
PRKCB	ENST00000321728.12 link	c.919-774A>T		intron_variant	Intron 8 of 16	1		ENSP00000318315.7		P05771-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21478

AN:

152144

Hom.:

1932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0487

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.144

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

GnomAD4 genome

AF:

0.141

AC:

21481

AN:

152262

Hom.:

1933

Cov.:

AF XY:

0.139

AC XY:

10332

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0451

AC:

1875

AN:

41566

American (AMR)

AF:

0.120

AC:

1829

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

601

AN:

3472

East Asian (EAS)

AF:

0.0488

AC:

253

AN:

5188

South Asian (SAS)

AF:

0.148

AC:

715

AN:

4826

European-Finnish (FIN)

AF:

0.171

AC:

1812

AN:

10590

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13959

AN:

68008

Other (OTH)

AF:

0.142

AC:

300

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

933

1865

2798

3730

4663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.174

Hom.:

343

Bravo

AF:

0.133

Asia WGS

AF:

0.0960

AC:

333

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.76

PhyloP100

-2.1

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