rs11649514

Variant names:

• chr16-24175240-G-T
• rs11649514
• NM_002738.7:c.1394+660G>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.1394+660G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,136 control chromosomes in the GnomAD database, including 436 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 0.067 (436 hom., cov: 31)
• Consequence: PRKCB NM_002738.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 7 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCB	NM_002738.7	c.1394+660G>T		intron_variant	Intron 12 of 16	ENST00000643927.1	NP_002729.2
PRKCB	NM_212535.3	c.1394+660G>T		intron_variant	Intron 12 of 16		NP_997700.1
PRKCB	XM_047434365.1	c.1007+660G>T		intron_variant	Intron 11 of 15		XP_047290321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCB	ENST00000643927.1	c.1394+660G>T		intron_variant	Intron 12 of 16		NM_002738.7	ENSP00000496129.1
PRKCB	ENST00000321728.12	c.1394+660G>T		intron_variant	Intron 12 of 16	1		ENSP00000318315.7
PRKCB	ENST00000472066.1	c.335+660G>T		intron_variant	Intron 4 of 4	3		ENSP00000457980.1
PRKCB	ENST00000487674.1	n.365+660G>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10225 AN: 152018 Hom.: 436 Cov.: 31

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0672 AC: 10223 AN: 152136 Hom.: 436 Cov.: 31 AF XY: 0.0660 AC XY: 4907 AN XY: 74386

African (AFR) AF: 0.0178 AC: 741 AN: 41552

American (AMR) AF: 0.0615 AC: 940 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.0709 AC: 363 AN: 5120

South Asian (SAS) AF: 0.120 AC: 579 AN: 4816

European-Finnish (FIN) AF: 0.0498 AC: 528 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6445 AN: 67972

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0847 Hom.: 1144

Bravo AF: 0.0651

Asia WGS AF: 0.0790 AC: 274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.8
DANN	Benign	0.88
PhyloP100		0.45
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: rs11649514; hg19: chr16-24186561;