Genetic Variant CPB2:c.*269G>C (chr13-46053345-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001872.5(CPB2):c.*269G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 306,836 control chromosomes in the GnomAD database, including 92,060 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.79 ( 47457 hom., cov: 31)

Exomes 𝑓: 0.76 ( 44603 hom. )

Consequence

CPB2
NM_001872.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

30 publications found

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 links:

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

CPB2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB2	NM_001872.5 link	c.*269G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000181383.10	NP_001863.3	Q96IY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10 link	c.*269G>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_001872.5	ENSP00000181383.4		Q96IY4-1

Frequencies

GnomAD3 genomes

AF:

0.787

AC:

119601

AN:

151968

Hom.:

47411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.804

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.749

GnomAD4 exome

AF:

0.756

AC:

117042

AN:

154750

Hom.:

44603

Cov.:

AF XY:

0.752

AC XY:

60024

AN XY:

79832

show subpopulations

African (AFR)

AF:

0.876

AC:

4904

AN:

5598

American (AMR)

AF:

0.793

AC:

5134

AN:

6472

Ashkenazi Jewish (ASJ)

AF:

0.702

AC:

3871

AN:

5512

East Asian (EAS)

AF:

0.838

AC:

10208

AN:

12176

South Asian (SAS)

AF:

0.703

AC:

5026

AN:

7154

European-Finnish (FIN)

AF:

0.832

AC:

5902

AN:

7096

Middle Eastern (MID)

AF:

0.662

AC:

498

AN:

752

European-Non Finnish (NFE)

AF:

0.740

AC:

74425

AN:

100516

Other (OTH)

AF:

0.747

AC:

7074

AN:

9474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1370

2740

4109

5479

6849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

602

1204

1806

2408

3010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.787

AC:

119702

AN:

152086

Hom.:

47457

Cov.:

AF XY:

0.789

AC XY:

58669

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.870

AC:

36093

AN:

41486

American (AMR)

AF:

0.774

AC:

11825

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2454

AN:

3470

East Asian (EAS)

AF:

0.804

AC:

4159

AN:

5176

South Asian (SAS)

AF:

0.708

AC:

3406

AN:

4808

European-Finnish (FIN)

AF:

0.828

AC:

8745

AN:

10560

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.745

AC:

50646

AN:

67992

Other (OTH)

AF:

0.750

AC:

1586

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1275

2551

3826

5102

6377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.786

Hom.:

5881

Bravo

AF:

0.786

Asia WGS

AF:

0.772

AC:

2685

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.5

(source)

DANN

Benign

0.88

PhyloP100

0.010

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over