chr13-46067331-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001872.5(CPB2):ā€‹c.678T>Cā€‹(p.Asp226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,553,388 control chromosomes in the GnomAD database, including 79,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.34 ( 9200 hom., cov: 32)
Exomes š‘“: 0.31 ( 70087 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.967
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 13-46067331-A-G is Benign according to our data. Variant chr13-46067331-A-G is described in ClinVar as [Benign]. Clinvar id is 3059117.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.967 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPB2NM_001872.5 linkuse as main transcriptc.678T>C p.Asp226= synonymous_variant 7/11 ENST00000181383.10
CPB2-AS1NR_046226.1 linkuse as main transcriptn.118+14366A>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.678T>C p.Asp226= synonymous_variant 7/111 NM_001872.5 P1Q96IY4-1
CPB2-AS1ENST00000663159.1 linkuse as main transcriptn.469+14366A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.343
AC:
52177
AN:
151950
Hom.:
9194
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.391
Gnomad AMI
AF:
0.288
Gnomad AMR
AF:
0.325
Gnomad ASJ
AF:
0.344
Gnomad EAS
AF:
0.257
Gnomad SAS
AF:
0.205
Gnomad FIN
AF:
0.398
Gnomad MID
AF:
0.370
Gnomad NFE
AF:
0.327
Gnomad OTH
AF:
0.348
GnomAD3 exomes
AF:
0.313
AC:
78482
AN:
250670
Hom.:
12676
AF XY:
0.308
AC XY:
41785
AN XY:
135512
show subpopulations
Gnomad AFR exome
AF:
0.387
Gnomad AMR exome
AF:
0.295
Gnomad ASJ exome
AF:
0.356
Gnomad EAS exome
AF:
0.261
Gnomad SAS exome
AF:
0.213
Gnomad FIN exome
AF:
0.399
Gnomad NFE exome
AF:
0.323
Gnomad OTH exome
AF:
0.313
GnomAD4 exome
AF:
0.312
AC:
436738
AN:
1401320
Hom.:
70087
Cov.:
25
AF XY:
0.310
AC XY:
217019
AN XY:
700450
show subpopulations
Gnomad4 AFR exome
AF:
0.384
Gnomad4 AMR exome
AF:
0.295
Gnomad4 ASJ exome
AF:
0.347
Gnomad4 EAS exome
AF:
0.257
Gnomad4 SAS exome
AF:
0.214
Gnomad4 FIN exome
AF:
0.394
Gnomad4 NFE exome
AF:
0.315
Gnomad4 OTH exome
AF:
0.314
GnomAD4 genome
AF:
0.343
AC:
52215
AN:
152068
Hom.:
9200
Cov.:
32
AF XY:
0.344
AC XY:
25561
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.391
Gnomad4 AMR
AF:
0.325
Gnomad4 ASJ
AF:
0.344
Gnomad4 EAS
AF:
0.258
Gnomad4 SAS
AF:
0.206
Gnomad4 FIN
AF:
0.398
Gnomad4 NFE
AF:
0.327
Gnomad4 OTH
AF:
0.347
Alfa
AF:
0.326
Hom.:
10354
Bravo
AF:
0.338
Asia WGS
AF:
0.262
AC:
912
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CPB2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 17, 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
-0.50
CADD
Benign
7.0
DANN
Benign
0.56

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: rs9316179; hg19: chr13-46641466; COSMIC: COSV51674341; API