rs10492795

Variant names:

• chr16-24004780-C-A
• rs10492795
• NM_002738.7:c.288+16190C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002738.7(PRKCB):​c.288+16190C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 152,250 control chromosomes in the GnomAD database, including 159 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 0.035 (159 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 6 publications found

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

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 = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.288+16190C>A		intron_variant	Intron 3 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.288+16190C>A		intron_variant	Intron 3 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-100+16190C>A		intron_variant	Intron 2 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.288+16190C>A		intron_variant	Intron 3 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.288+16190C>A		intron_variant	Intron 3 of 16	1		ENSP00000318315.7
PRKCB	ENST00000498739.1	c.-26-88011C>A		intron_variant	Intron 1 of 3	4		ENSP00000459227.1
PRKCB	ENST00000647422.1	n.188+16190C>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5291 AN: 152132 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0312

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

GnomAD4 genome AF: 0.0347 AC: 5288 AN: 152250 Hom.: 159 Cov.: 32 AF XY: 0.0341 AC XY: 2538 AN XY: 74430

African (AFR) AF: 0.00840 AC: 349 AN: 41548

American (AMR) AF: 0.0277 AC: 424 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4824

European-Finnish (FIN) AF: 0.0473 AC: 501 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3651 AN: 68020

Other (OTH) AF: 0.0308 AC: 65 AN: 2108

Alfa AF: 0.0483 Hom.: 602

Bravo AF: 0.0315

Asia WGS AF: 0.0180 AC: 64 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	0.30
DANN	Benign	0.37
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10492795; hg19: chr16-24016101;