Menu
GeneBe

13-46064709-A-G

Variant summary

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

The NM_001872.5(CPB2):c.735T>C(p.Tyr245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,188 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204
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=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-46064709-A-G is Benign according to our data. Variant chr13-46064709-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 713135.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=-0.204 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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPB2NM_001872.5 linkuse as main transcriptc.735T>C p.Tyr245= synonymous_variant 8/11 ENST00000181383.10
CPB2-AS1NR_046226.1 linkuse as main transcriptn.118+11744A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPB2ENST00000181383.10 linkuse as main transcriptc.735T>C p.Tyr245= synonymous_variant 8/111 NM_001872.5 P1Q96IY4-1
CPB2-AS1ENST00000663159.1 linkuse as main transcriptn.469+11744A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00125
AC:
190
AN:
152266
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.0202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00123
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00155
AC:
391
AN:
251462
Hom.:
0
AF XY:
0.00141
AC XY:
191
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.0197
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000785
Gnomad NFE exome
AF:
0.00113
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00130
AC:
1900
AN:
1461804
Hom.:
3
Cov.:
30
AF XY:
0.00127
AC XY:
921
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000827
Gnomad4 ASJ exome
AF:
0.0197
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000618
Gnomad4 NFE exome
AF:
0.00101
Gnomad4 OTH exome
AF:
0.00235
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00125
AC:
190
AN:
152384
Hom.:
2
Cov.:
31
AF XY:
0.00123
AC XY:
92
AN XY:
74522
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.00123
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00262
Hom.:
0
Bravo
AF:
0.00116
Asia WGS
AF:
0.000577
AC:
3
AN:
3478
EpiCase
AF:
0.000927
EpiControl
AF:
0.00160

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
1.1
Dann
Benign
0.29

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: rs145262149; hg19: chr13-46638844; API