rs1015408

Variant names:

• chr16-24199041-T-A
• rs1015408
• NM_002738.7:c.1863+7811T>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.1863+7811T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,188 control chromosomes in the GnomAD database, including 2,732 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 (2732 hom., cov: 32)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 3 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 = 0.217 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.1863+7811T>A		intron	N/A	NP_002729.2
	PRKCB	NM_212535.3		c.1863+7811T>A		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.1863+7811T>A		intron	N/A	ENSP00000496129.1
	PRKCB	ENST00000321728.12	TSL:1	c.1863+7811T>A		intron	N/A	ENSP00000318315.7

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26622 AN: 152070 Hom.: 2728 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.175 AC: 26630 AN: 152188 Hom.: 2732 Cov.: 32 AF XY: 0.178 AC XY: 13223 AN XY: 74386

African (AFR) AF: 0.0770 AC: 3198 AN: 41536

American (AMR) AF: 0.223 AC: 3408 AN: 15290

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

East Asian (EAS) AF: 0.224 AC: 1161 AN: 5188

South Asian (SAS) AF: 0.162 AC: 780 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2655 AN: 10584

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

European-Non Finnish (NFE) AF: 0.212 AC: 14430 AN: 67994

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.187 Hom.: 362

Bravo AF: 0.168

Asia WGS AF: 0.210 AC: 729 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	0.21
DANN	Benign	0.65
PhyloP100		-0.25
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: rs1015408; hg19: chr16-24210362;