chr13-46082277-T-G

Variant names:

• chr13-46082277-T-G
• rs3818477
• NM_001872.5:c.384+164A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001872.5(CPB2):​c.384+164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,986 control chromosomes in the GnomAD database, including 11,425 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 (11425 hom., cov: 32)
• Consequence: CPB2 NM_001872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB2	NM_001872.5	c.384+164A>C		intron_variant	Intron 4 of 10	ENST00000181383.10	NP_001863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10	c.384+164A>C		intron_variant	Intron 4 of 10	1	NM_001872.5	ENSP00000181383.4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57781 AN: 151868 Hom.: 11420 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.380 AC: 57818 AN: 151986 Hom.: 11425 Cov.: 32 AF XY: 0.384 AC XY: 28535 AN XY: 74286

African (AFR) AF: 0.316 AC: 13113 AN: 41442

American (AMR) AF: 0.416 AC: 6354 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1001 AN: 3468

East Asian (EAS) AF: 0.628 AC: 3245 AN: 5166

South Asian (SAS) AF: 0.490 AC: 2361 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4137 AN: 10550

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26439 AN: 67958

Other (OTH) AF: 0.357 AC: 753 AN: 2112

Alfa AF: 0.376 Hom.: 14694

Bravo AF: 0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.68
PhyloP100		-2.1
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: rs3818477; hg19: chr13-46656412; COSMIC: COSV51675631;