Genetic Variant CPB2:c.*310T>A (chr13-46053304-A-T) – 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.*310T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 234,868 control chromosomes in the GnomAD database, including 13,168 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 0.33 ( 8526 hom., cov: 32)

Exomes 𝑓: 0.32 ( 4642 hom. )

Consequence

CPB2
NM_001872.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.646

Publications

19 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB2	NM_001872.5 link	c.*310T>A		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.*310T>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001872.5	ENSP00000181383.4		Q96IY4-1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50302

AN:

151998

Hom.:

8525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.323

AC:

26732

AN:

82752

Hom.:

4642

Cov.:

AF XY:

0.318

AC XY:

13676

AN XY:

43032

show subpopulations

African (AFR)

AF:

0.316

AC:

1007

AN:

3186

American (AMR)

AF:

0.303

AC:

1331

AN:

4388

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1046

AN:

3042

East Asian (EAS)

AF:

0.254

AC:

1596

AN:

6276

South Asian (SAS)

AF:

0.201

AC:

1090

AN:

5412

European-Finnish (FIN)

AF:

0.411

AC:

1313

AN:

3196

Middle Eastern (MID)

AF:

0.337

AC:

137

AN:

406

European-Non Finnish (NFE)

AF:

0.340

AC:

17647

AN:

51852

Other (OTH)

AF:

0.313

AC:

1565

AN:

4994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

871

1742

2613

3484

4355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.331

AC:

50329

AN:

152116

Hom.:

8526

Cov.:

AF XY:

0.332

AC XY:

24667

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.318

AC:

13181

AN:

41488

American (AMR)

AF:

0.321

AC:

4901

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1164

AN:

3468

East Asian (EAS)

AF:

0.256

AC:

1328

AN:

5178

South Asian (SAS)

AF:

0.203

AC:

979

AN:

4832

European-Finnish (FIN)

AF:

0.427

AC:

4509

AN:

10550

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23100

AN:

67994

Other (OTH)

AF:

0.339

AC:

717

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1748

3496

5243

6991

8739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.238

Hom.:

681

Bravo

AF:

0.320

Asia WGS

AF:

0.256

AC:

890

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.2

(source)

DANN

Benign

0.47

PhyloP100

-0.65

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

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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