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GeneBe

13-46064691-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001872.5(CPB2):c.753C>T(p.Ile251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,613,616 control chromosomes in the GnomAD database, including 7,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.094 ( 869 hom., cov: 32)
Exomes 𝑓: 0.079 ( 6179 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-46064691-G-A is Benign according to our data. Variant chr13-46064691-G-A is described in ClinVar as [Benign]. Clinvar id is 3059439.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.18 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPB2NM_001872.5 linkuse as main transcriptc.753C>T p.Ile251= synonymous_variant 8/11 ENST00000181383.10
CPB2-AS1NR_046226.1 linkuse as main transcriptn.118+11726G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPB2ENST00000181383.10 linkuse as main transcriptc.753C>T p.Ile251= synonymous_variant 8/111 NM_001872.5 P1Q96IY4-1
CPB2-AS1ENST00000663159.1 linkuse as main transcriptn.469+11726G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0946
AC:
14390
AN:
152086
Hom.:
871
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.118
Gnomad AMI
AF:
0.0373
Gnomad AMR
AF:
0.136
Gnomad ASJ
AF:
0.0706
Gnomad EAS
AF:
0.287
Gnomad SAS
AF:
0.123
Gnomad FIN
AF:
0.0422
Gnomad MID
AF:
0.0854
Gnomad NFE
AF:
0.0645
Gnomad OTH
AF:
0.100
GnomAD3 exomes
AF:
0.109
AC:
27302
AN:
251388
Hom.:
2218
AF XY:
0.103
AC XY:
14038
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.120
Gnomad AMR exome
AF:
0.196
Gnomad ASJ exome
AF:
0.0695
Gnomad EAS exome
AF:
0.304
Gnomad SAS exome
AF:
0.115
Gnomad FIN exome
AF:
0.0424
Gnomad NFE exome
AF:
0.0639
Gnomad OTH exome
AF:
0.0949
GnomAD4 exome
AF:
0.0790
AC:
115472
AN:
1461412
Hom.:
6179
Cov.:
31
AF XY:
0.0791
AC XY:
57521
AN XY:
727036
show subpopulations
Gnomad4 AFR exome
AF:
0.114
Gnomad4 AMR exome
AF:
0.192
Gnomad4 ASJ exome
AF:
0.0700
Gnomad4 EAS exome
AF:
0.288
Gnomad4 SAS exome
AF:
0.114
Gnomad4 FIN exome
AF:
0.0416
Gnomad4 NFE exome
AF:
0.0645
Gnomad4 OTH exome
AF:
0.0915
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0945
AC:
14381
AN:
152204
Hom.:
869
Cov.:
32
AF XY:
0.0945
AC XY:
7029
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.118
Gnomad4 AMR
AF:
0.136
Gnomad4 ASJ
AF:
0.0706
Gnomad4 EAS
AF:
0.286
Gnomad4 SAS
AF:
0.122
Gnomad4 FIN
AF:
0.0422
Gnomad4 NFE
AF:
0.0645
Gnomad4 OTH
AF:
0.0985
Alfa
AF:
0.0724
Hom.:
629
Bravo
AF:
0.107
Asia WGS
AF:
0.180
AC:
623
AN:
3478
EpiCase
AF:
0.0651
EpiControl
AF:
0.0679

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CPB2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 19, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
0.85
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2277440; hg19: chr13-46638826; COSMIC: COSV51672963; API