chr13-46084238-C-T

Position:

• chr13-46084238-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001872.5(CPB2):​c.256G>A​(p.Val86Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 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: 0.947

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0758585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPB2	NM_001872.5	c.256G>A	p.Val86Met	missense_variant	3/11	ENST00000181383.10	NP_001863.3
CPB2-AS1	NR_046226.1	n.119-10615C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10	c.256G>A	p.Val86Met	missense_variant	3/11	1	NM_001872.5	ENSP00000181383	P1
CPB2-AS1	ENST00000663159.1	n.469+31273C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 05, 2024

The c.256G>A (p.V86M) alteration is located in exon 3 (coding exon 3) of the CPB2 gene. This alteration results from a G to A substitution at nucleotide position 256, causing the valine (V) at amino acid position 86 to be replaced by a methionine (M). 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	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.048	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.57	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N;N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.61	.;N;N
REVEL	Benign	0.075
Sift	Uncertain	0.022	.;D;D
Sift4G	Uncertain	0.027	.;D;D
Polyphen		0.0030	B;B;.
Vest4		0.24, 0.25
MutPred		0.38		Loss of glycosylation at S87 (P = 0.1477);Loss of glycosylation at S87 (P = 0.1477);Loss of glycosylation at S87 (P = 0.1477);
MVP		0.15
MPC		0.39
ClinPred		0.12	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-46658373;