16-23876862-G-T

Variant names:

• chr16-23876862-G-T
• rs9940072
• NM_002738.7:c.205+39456G>T

Variant summary

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

The NM_002738.7(PRKCB):​c.205+39456G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,082 control chromosomes in the GnomAD database, including 18,947 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 0.49 (18947 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002738.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	NM_002738.7	MANE Select	c.205+39456G>T		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.205+39456G>T		intron	N/A	NP_997700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCB	ENST00000643927.1	MANE Select	c.205+39456G>T		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.205+39456G>T		intron	N/A	ENSP00000318315.7
	PRKCB	ENST00000498739.1	TSL:4	c.-27+39456G>T		intron	N/A	ENSP00000459227.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74799 AN: 151964 Hom.: 18929 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.492 AC: 74844 AN: 152082 Hom.: 18947 Cov.: 32 AF XY: 0.497 AC XY: 36953 AN XY: 74336

African (AFR) AF: 0.400 AC: 16599 AN: 41462

American (AMR) AF: 0.583 AC: 8906 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1497 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3193 AN: 5170

South Asian (SAS) AF: 0.353 AC: 1702 AN: 4824

European-Finnish (FIN) AF: 0.614 AC: 6493 AN: 10572

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34904 AN: 68004

Other (OTH) AF: 0.492 AC: 1037 AN: 2108

Alfa AF: 0.513 Hom.: 3231

Bravo AF: 0.488

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.40
PhyloP100		0.77
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: rs9940072; hg19: chr16-23888183;