16-23898631-T-G

Variant names:

• chr16-23898631-T-G
• rs9922316
• NM_002738.7:c.205+61225T>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.205+61225T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,120 control chromosomes in the GnomAD database, including 46,997 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 0.78 (46997 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.205+61225T>G		intron_variant	Intron 2 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.205+61225T>G		intron_variant	Intron 2 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-183+58672T>G		intron_variant	Intron 1 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.205+61225T>G		intron_variant	Intron 2 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.205+61225T>G		intron_variant	Intron 2 of 16	1		ENSP00000318315.7
PRKCB	ENST00000498739.1	c.-27+61225T>G		intron_variant	Intron 1 of 3	4		ENSP00000459227.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118569 AN: 152002 Hom.: 46983 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.780 AC: 118628 AN: 152120 Hom.: 46997 Cov.: 31 AF XY: 0.784 AC XY: 58302 AN XY: 74372

African (AFR) AF: 0.623 AC: 25826 AN: 41444

American (AMR) AF: 0.830 AC: 12693 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2914 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5138 AN: 5186

South Asian (SAS) AF: 0.925 AC: 4458 AN: 4822

European-Finnish (FIN) AF: 0.837 AC: 8870 AN: 10598

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56131 AN: 67996

Other (OTH) AF: 0.786 AC: 1654 AN: 2104

Alfa AF: 0.811 Hom.: 101241

Bravo AF: 0.776

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.95
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: rs9922316; hg19: chr16-23909952;