13-46053304-A-T

Position:

• chr13-46053304-A-T

Variant summary

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

The NM_001872.5(CPB2):​c.*310T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 234,868 control chromosomes in the GnomAD database, including 13,168 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 0.33 (8526 hom., cov: 32)
  • Exomes 𝑓: 0.32 (4642 hom.)
• Consequence: CPB2 NM_001872.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPB2	NM_001872.5	c.*310T>A		3_prime_UTR_variant	11/11	ENST00000181383.10	NP_001863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383	c.*310T>A		3_prime_UTR_variant	11/11	1	NM_001872.5	ENSP00000181383.4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50302 AN: 151998 Hom.: 8525 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.323 AC: 26732 AN: 82752 Hom.: 4642 Cov.: 2 AF XY: 0.318 AC XY: 13676 AN XY: 43032

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.331 AC: 50329 AN: 152116 Hom.: 8526 Cov.: 32 AF XY: 0.332 AC XY: 24667 AN XY: 74344

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.339

Alfa AF: 0.238 Hom.: 681

Bravo AF: 0.320

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.47

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: rs1087; hg19: chr13-46627439;