rs11074606

Variant names:

• chr16-24121248-A-G
• rs11074606
• NM_002738.7:c.919-2587A>G

Variant summary

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

The NM_002738.7(PRKCB):​c.919-2587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,098 control chromosomes in the GnomAD database, including 8,438 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 0.32 (8438 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.919-2587A>G		intron_variant	Intron 8 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.919-2587A>G		intron_variant	Intron 8 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.532-2587A>G		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	c.919-2587A>G		intron_variant	Intron 8 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.919-2587A>G		intron_variant	Intron 8 of 16	1		ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48242 AN: 151980 Hom.: 8440 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.317 AC: 48237 AN: 152098 Hom.: 8438 Cov.: 32 AF XY: 0.325 AC XY: 24127 AN XY: 74336

African (AFR) AF: 0.212 AC: 8795 AN: 41508

American (AMR) AF: 0.300 AC: 4584 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3702 AN: 5158

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3961 AN: 10566

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22658 AN: 67980

Other (OTH) AF: 0.340 AC: 719 AN: 2114

Alfa AF: 0.330 Hom.: 3404

Bravo AF: 0.307

Asia WGS AF: 0.550 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.62
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs11074606; hg19: chr16-24132569;