chr16-24203631-T-G

Variant names:

• chr16-24203631-T-G
• rs10492797
• NM_002738.7:c.1864-11027T>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.1864-11027T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,082 control chromosomes in the GnomAD database, including 2,648 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 0.17 (2648 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 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.1864-11027T>G		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.1863+12401T>G		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.1864-11027T>G		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.1863+12401T>G		intron	N/A	ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25914 AN: 151964 Hom.: 2645 Cov.: 31

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.170 AC: 25916 AN: 152082 Hom.: 2648 Cov.: 31 AF XY: 0.174 AC XY: 12910 AN XY: 74346

African (AFR) AF: 0.0644 AC: 2674 AN: 41520

American (AMR) AF: 0.219 AC: 3350 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5156

South Asian (SAS) AF: 0.161 AC: 773 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2652 AN: 10562

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14337 AN: 67966

Other (OTH) AF: 0.177 AC: 374 AN: 2108

Alfa AF: 0.190 Hom.: 7950

Bravo AF: 0.163

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.61
PhyloP100		-0.064
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: rs10492797; hg19: chr16-24214952;