dbSNP rs17844078: CPB2:c.591+3184T>C (chr13-46070689-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001872.5(CPB2):c.591+3184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,324 control chromosomes in the GnomAD database, including 82 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 0.027 ( 82 hom., cov: 32)

Consequence

CPB2
NM_001872.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Publications

3 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=-0.87).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.027 (4114/152324) while in subpopulation NFE AF = 0.042 (2857/68024). AF 95% confidence interval is 0.0407. There are 82 homozygotes in GnomAd4. There are 1926 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 82 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPB2	NM_001872.5	MANE Select	c.591+3184T>C	intron	N/A	NP_001863.3	Q96IY4-1
CPB2	NM_001278541.2		c.591+3184T>C	intron	N/A	NP_001265470.1	A0A087WSY5
CPB2-AS1	NR_046226.1		n.118+17724A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPB2	ENST00000181383.10	TSL:1 MANE Select	c.591+3184T>C	intron	N/A	ENSP00000181383.4	Q96IY4-1
CPB2	ENST00000674625.1		c.*2781T>C	3_prime_UTR	Exon 7 of 7	ENSP00000502808.1	A0A6Q8PHS9
CPB2	ENST00000882332.1		c.693+3184T>C	intron	N/A	ENSP00000552391.1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4115

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.0440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0270

AC:

4114

AN:

152324

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1926

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00864

AC:

359

AN:

41564

American (AMR)

AF:

0.0293

AC:

448

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0382

AC:

184

AN:

4822

European-Finnish (FIN)

AF:

0.00640

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2857

AN:

68024

Other (OTH)

AF:

0.0435

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

207

415

622

830

1037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0329

Hom.:

Bravo

AF:

0.0284

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

(source)

DANN

Benign

0.76

PhyloP100

-0.060

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over