NM_001872.5:c.511A>G

Variant names:

• chr13-46073953-T-C
• rs1193282604
• NM_001872.5:c.511A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001872.5(CPB2):​c.511A>G​(p.Lys171Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,437,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CPB2 NM_001872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.511A>G	p.Lys171Glu	missense	Exon 6 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.511A>G	p.Lys171Glu	missense	Exon 6 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.119-20900T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.511A>G	p.Lys171Glu	missense	Exon 6 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.613A>G	p.Lys205Glu	missense	Exon 6 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.559A>G	p.Lys187Glu	missense	Exon 6 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251132 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437436 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 711880

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092656

Other (OTH) AF: 0.00 AC: 0 AN: 59112

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		6.9
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.97	D
Vest4		0.43
MutPred		0.64		Loss of methylation at K171 (P = 0.0071)
MVP		0.72
MPC		1.2
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.90
gMVP		0.95
Mutation Taster		=72/28	polymorphism

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: rs1193282604; hg19: chr13-46648088;