rs1059502

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001871.3(CPB1):c.622G>A(p.Asp208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,612,786 control chromosomes in the GnomAD database, including 44,685 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D208A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.24 ( 4630 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40055 hom. )

Consequence

CPB1
NM_001871.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.624

Publications

28 publications found

Variant links:

Genes affected

CPB1 (HGNC:2299): (carboxypeptidase B1) Three different procarboxypeptidases A and two different procarboxypeptidases B have been isolated. The B1 and B2 forms differ from each other mainly in isoelectric point. Carboxypeptidase B1 is a highly tissue-specific protein and is a useful serum marker for acute pancreatitis and dysfunction of pancreatic transplants. It is not elevated in pancreatic carcinoma. [provided by RefSeq, Jul 2008]

CPB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.2314997E-4).

BP6

Variant 3-148844523-G-A is Benign according to our data. Variant chr3-148844523-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059113.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB1	NM_001871.3 link	c.622G>A	p.Asp208Asn	missense_variant	Exon 7 of 11	ENST00000282957.9	NP_001862.2	P15086

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPB1	ENST00000282957.9 link	c.622G>A	p.Asp208Asn	missense_variant	Exon 7 of 11	1	NM_001871.3	ENSP00000282957.4	P15086
CPB1	ENST00000491148.5 link	c.622G>A	p.Asp208Asn	missense_variant	Exon 8 of 12	5		ENSP00000417222.1	P15086
CPB1	ENST00000468341.1 link	c.520G>A	p.Asp174Asn	missense_variant	Exon 6 of 7	3		ENSP00000419427.1	C9JUX7
CPB1	ENST00000484877.1 link	n.*27G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37011

AN:

151944

Hom.:

4624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.214

GnomAD2 exomes

AF:

0.224

AC:

56168

AN:

250960

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.231

AC:

337317

AN:

1460724

Hom.:

40055

Cov.:

AF XY:

0.232

AC XY:

168553

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.311

AC:

10411

AN:

33442

American (AMR)

AF:

0.152

AC:

6780

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3317

AN:

26114

East Asian (EAS)

AF:

0.240

AC:

9514

AN:

39686

South Asian (SAS)

AF:

0.282

AC:

24319

AN:

86208

European-Finnish (FIN)

AF:

0.230

AC:

12281

AN:

53398

Middle Eastern (MID)

AF:

0.109

AC:

630

AN:

5766

European-Non Finnish (NFE)

AF:

0.231

AC:

256821

AN:

1111056

Other (OTH)

AF:

0.219

AC:

13244

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

12843

25686

38528

51371

64214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9002

18004

27006

36008

45010

<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:

0.244

AC:

37036

AN:

152062

Hom.:

4630

Cov.:

AF XY:

0.242

AC XY:

17955

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.308

AC:

12789

AN:

41482

American (AMR)

AF:

0.176

AC:

2689

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3468

East Asian (EAS)

AF:

0.255

AC:

1316

AN:

5166

South Asian (SAS)

AF:

0.285

AC:

1374

AN:

4818

European-Finnish (FIN)

AF:

0.237

AC:

2504

AN:

10578

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15168

AN:

67984

Other (OTH)

AF:

0.215

AC:

454

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1446

2893

4339

5786

7232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.223

Hom.:

13204

Bravo

AF:

0.239

TwinsUK

AF:

0.239

AC:

888

ALSPAC

AF:

0.226

AC:

871

ESP6500AA

AF:

0.308

AC:

1358

ESP6500EA

AF:

0.206

AC:

1769

ExAC

AF:

0.229

AC:

27749

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

EpiCase

AF:

0.208

EpiControl

AF:

0.205

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CPB1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.24

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.037

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.45

.;T;T

MetaRNN

Benign

0.00052

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.67

N;N;.

PhyloP100

-0.62

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.88

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.045

MPC

0.20

ClinPred

0.00085

GERP RS

-2.8

Varity_R

0.047

gMVP

0.75

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over