chr13-46084577-A-G

Variant names:

• chr13-46084577-A-G
• rs7336399
• NM_001872.5:c.151-234T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001872.5(CPB2):​c.151-234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,942 control chromosomes in the GnomAD database, including 11,619 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 0.38 (11619 hom., cov: 32)
• Consequence: CPB2 NM_001872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

Genes affected

CPB2 (HGNC:2300): (carboxypeptidase B2) Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by trypsin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and its promoter region. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB2	NM_001872.5	c.151-234T>C		intron_variant	Intron 2 of 10	ENST00000181383.10	NP_001863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10	c.151-234T>C		intron_variant	Intron 2 of 10	1	NM_001872.5	ENSP00000181383.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58315 AN: 151824 Hom.: 11614 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.384 AC: 58349 AN: 151942 Hom.: 11619 Cov.: 32 AF XY: 0.387 AC XY: 28768 AN XY: 74260

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.362

Alfa AF: 0.391 Hom.: 11355

Bravo AF: 0.387

Asia WGS AF: 0.506 AC: 1756 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7336399; hg19: chr13-46658712;