16-24042370-T-C

Variant names:

• chr16-24042370-T-C
• rs11074601
• NM_002738.7:c.529+6823T>C

Variant summary

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

The NM_002738.7(PRKCB):​c.529+6823T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,992 control chromosomes in the GnomAD database, including 22,951 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 0.55 (22951 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.529+6823T>C		intron_variant	Intron 5 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.529+6823T>C		intron_variant	Intron 5 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.142+6823T>C		intron_variant	Intron 4 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.529+6823T>C		intron_variant	Intron 5 of 16		NM_002738.7	ENSP00000496129.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83160 AN: 151876 Hom.: 22923 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.548 AC: 83239 AN: 151992 Hom.: 22951 Cov.: 32 AF XY: 0.549 AC XY: 40773 AN XY: 74290

African (AFR) AF: 0.542 AC: 22461 AN: 41430

American (AMR) AF: 0.627 AC: 9581 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2214 AN: 3464

East Asian (EAS) AF: 0.579 AC: 2987 AN: 5162

South Asian (SAS) AF: 0.693 AC: 3338 AN: 4816

European-Finnish (FIN) AF: 0.496 AC: 5236 AN: 10560

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35602 AN: 67968

Other (OTH) AF: 0.570 AC: 1204 AN: 2112

Alfa AF: 0.534 Hom.: 49789

Bravo AF: 0.557

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		-0.037
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: rs11074601; hg19: chr16-24053691; COSMIC: COSV57803382;