13-46073959-C-T

Variant names:

• chr13-46073959-C-T
• rs3742264
• NM_001872.5:c.505G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001872.5(CPB2):​c.505G>A​(p.Ala169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,578,308 control chromosomes in the GnomAD database, including 83,515 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9111 hom., cov: 30)
  • Exomes 𝑓: 0.32 (74404 hom.)
• Consequence: CPB2 NM_001872.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.748
• Publications: 88 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023388267).
• BP6: Variant 13-46073959-C-T is Benign according to our data. Variant chr13-46073959-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059667.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	NM_001872.5	MANE Select	c.505G>A	p.Ala169Thr	missense	Exon 6 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.505G>A	p.Ala169Thr	missense	Exon 6 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.119-20894C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.505G>A	p.Ala169Thr	missense	Exon 6 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.607G>A	p.Ala203Thr	missense	Exon 6 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.553G>A	p.Ala185Thr	missense	Exon 6 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51867 AN: 151216 Hom.: 9105 Cov.: 30

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.312 AC: 78096 AN: 250340 AF XY: 0.308

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.319 AC: 455760 AN: 1426978 Hom.: 74404 Cov.: 31 AF XY: 0.316 AC XY: 223469 AN XY: 706124

African (AFR) AF: 0.390 AC: 12875 AN: 33034

American (AMR) AF: 0.290 AC: 12818 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 8846 AN: 25394

East Asian (EAS) AF: 0.257 AC: 10020 AN: 39050

South Asian (SAS) AF: 0.215 AC: 18008 AN: 83702

European-Finnish (FIN) AF: 0.393 AC: 20675 AN: 52568

Middle Eastern (MID) AF: 0.317 AC: 1784 AN: 5636

European-Non Finnish (NFE) AF: 0.324 AC: 351980 AN: 1084800

Other (OTH) AF: 0.320 AC: 18754 AN: 58528

GnomAD4 genome AF: 0.343 AC: 51903 AN: 151330 Hom.: 9111 Cov.: 30 AF XY: 0.343 AC XY: 25377 AN XY: 73894

African (AFR) AF: 0.390 AC: 16076 AN: 41172

American (AMR) AF: 0.324 AC: 4925 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3460

East Asian (EAS) AF: 0.251 AC: 1273 AN: 5072

South Asian (SAS) AF: 0.207 AC: 996 AN: 4812

European-Finnish (FIN) AF: 0.399 AC: 4137 AN: 10370

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.327 AC: 22217 AN: 67926

Other (OTH) AF: 0.344 AC: 721 AN: 2098

Alfa AF: 0.328 Hom.: 28757

Bravo AF: 0.337

TwinsUK AF: 0.316 AC: 1172

ALSPAC AF: 0.332 AC: 1278

ESP6500AA AF: 0.389 AC: 1714

ESP6500EA AF: 0.323 AC: 2782

ExAC AF: 0.310 AC: 37644

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CPB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.78
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00088	N
LIST_S2	Benign	0.040	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.0	N
PhyloP100		0.75
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.024
Sift	Benign	0.61	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.37
ClinPred		0.0018	T
GERP RS		2.7
Varity_R		0.15
gMVP		0.56
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: rs3742264; hg19: chr13-46648094; COSMIC: COSV51674355;