13-46082511-T-C

Position:

• chr13-46082511-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001872.5(CPB2):​c.314A>G​(p.Gln105Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPB2 NM_001872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPB2	NM_001872.5	c.314A>G	p.Gln105Arg	missense_variant	4/11	ENST00000181383.10
CPB2-AS1	NR_046226.1	n.119-12342T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPB2	ENST00000181383.10	c.314A>G	p.Gln105Arg	missense_variant	4/11	1	NM_001872.5	P1
CPB2-AS1	ENST00000663159.1	n.469+29546T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.314A>G (p.Q105R) alteration is located in exon 4 (coding exon 4) of the CPB2 gene. This alteration results from a A to G substitution at nucleotide position 314, causing the glutamine (Q) at amino acid position 105 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	.;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.0030	.;D;D
Polyphen		1.0	D;D;.
Vest4		0.52, 0.54
MutPred		0.56		Gain of catalytic residue at Q105 (P = 0.0334);Gain of catalytic residue at Q105 (P = 0.0334);Gain of catalytic residue at Q105 (P = 0.0334);
MVP		0.52
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-46656646;