rs16972959

Variant names:

• chr16-23890055-G-A
• rs16972959
• NM_002738.7:c.205+52649G>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.205+52649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,168 control chromosomes in the GnomAD database, including 2,180 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 0.15 (2180 hom., cov: 33)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 11 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 = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.205+52649G>A		intron_variant	Intron 2 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.205+52649G>A		intron_variant	Intron 2 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.-183+50096G>A		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+52649G>A		intron_variant	Intron 2 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.205+52649G>A		intron_variant	Intron 2 of 16	1		ENSP00000318315.7
PRKCB	ENST00000498739.1	c.-27+52649G>A		intron_variant	Intron 1 of 3	4		ENSP00000459227.1
PRKCB	ENST00000645517.1	n.153-2909G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23094 AN: 152050 Hom.: 2175 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.152 AC: 23099 AN: 152168 Hom.: 2180 Cov.: 33 AF XY: 0.150 AC XY: 11182 AN XY: 74396

African (AFR) AF: 0.0476 AC: 1977 AN: 41528

American (AMR) AF: 0.150 AC: 2298 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1205 AN: 5168

South Asian (SAS) AF: 0.199 AC: 963 AN: 4828

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10582

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13389 AN: 67996

Other (OTH) AF: 0.164 AC: 346 AN: 2112

Alfa AF: 0.181 Hom.: 2312

Bravo AF: 0.151

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.39
PhyloP100		0.040
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: rs16972959; hg19: chr16-23901376;