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GeneBe

13-46073912-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001872.5(CPB2):c.552A>G(p.Glu184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,590,332 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 28)
Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.256
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-46073912-T-C is Benign according to our data. Variant chr13-46073912-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039073.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=0.256 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPB2NM_001872.5 linkuse as main transcriptc.552A>G p.Glu184= synonymous_variant 6/11 ENST00000181383.10
CPB2-AS1NR_046226.1 linkuse as main transcriptn.119-20941T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPB2ENST00000181383.10 linkuse as main transcriptc.552A>G p.Glu184= synonymous_variant 6/111 NM_001872.5 P1Q96IY4-1
CPB2-AS1ENST00000663159.1 linkuse as main transcriptn.469+20947T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000389
AC:
59
AN:
151700
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000460
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000482
AC:
121
AN:
251284
Hom.:
2
AF XY:
0.000486
AC XY:
66
AN XY:
135814
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000666
Gnomad ASJ exome
AF:
0.00189
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000590
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000426
AC:
613
AN:
1438516
Hom.:
3
Cov.:
29
AF XY:
0.000436
AC XY:
311
AN XY:
712794
show subpopulations
Gnomad4 AFR exome
AF:
0.0000601
Gnomad4 AMR exome
AF:
0.000584
Gnomad4 ASJ exome
AF:
0.00152
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000225
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000371
Gnomad4 OTH exome
AF:
0.000880
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000389
AC:
59
AN:
151816
Hom.:
0
Cov.:
28
AF XY:
0.000337
AC XY:
25
AN XY:
74186
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000459
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000486
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000540
Hom.:
0
Bravo
AF:
0.000472
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

CPB2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 18, 2019This variant is classified as likely 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
-0.52
Cadd
Benign
5.8
Dann
Benign
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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

LitVar

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

Other links and lift over

dbSNP: rs200231942; hg19: chr13-46648047; API