rs2296642

Variant names:

• chr13-46082534-A-G
• rs2296642
• NM_001872.5:c.291T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001872.5(CPB2):​c.291T>C​(p.Asp97Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,609,964 control chromosomes in the GnomAD database, including 455,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.78 (46948 hom., cov: 31)
  • Exomes 𝑓: 0.75 (408263 hom.)
• Consequence: CPB2 NM_001872.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.01
• Publications: 22 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 13-46082534-A-G is Benign according to our data. Variant chr13-46082534-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060878.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	NM_001872.5	MANE Select	c.291T>C	p.Asp97Asp	synonymous	Exon 4 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.291T>C	p.Asp97Asp	synonymous	Exon 4 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.119-12319A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.291T>C	p.Asp97Asp	synonymous	Exon 4 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.393T>C	p.Asp131Asp	synonymous	Exon 4 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.339T>C	p.Asp113Asp	synonymous	Exon 4 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119045 AN: 151998 Hom.: 46911 Cov.: 31

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.744

GnomAD2 exomes AF: 0.764 AC: 191814 AN: 251136 AF XY: 0.756

Gnomad AFR exome AF: 0.864

Gnomad AMR exome AF: 0.813

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.822

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.737

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.747 AC: 1089034 AN: 1457848 Hom.: 408263 Cov.: 32 AF XY: 0.745 AC XY: 540488 AN XY: 725450

African (AFR) AF: 0.864 AC: 28897 AN: 33436

American (AMR) AF: 0.810 AC: 36212 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18319 AN: 26082

East Asian (EAS) AF: 0.843 AC: 33403 AN: 39638

South Asian (SAS) AF: 0.710 AC: 61071 AN: 86066

European-Finnish (FIN) AF: 0.814 AC: 43424 AN: 53362

Middle Eastern (MID) AF: 0.685 AC: 3944 AN: 5758

European-Non Finnish (NFE) AF: 0.739 AC: 819067 AN: 1108586

Other (OTH) AF: 0.742 AC: 44697 AN: 60240

GnomAD4 genome AF: 0.783 AC: 119138 AN: 152116 Hom.: 46948 Cov.: 31 AF XY: 0.785 AC XY: 58352 AN XY: 74362

African (AFR) AF: 0.860 AC: 35692 AN: 41484

American (AMR) AF: 0.772 AC: 11803 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2450 AN: 3472

East Asian (EAS) AF: 0.812 AC: 4206 AN: 5178

South Asian (SAS) AF: 0.713 AC: 3437 AN: 4820

European-Finnish (FIN) AF: 0.813 AC: 8595 AN: 10570

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50585 AN: 67996

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.751 Hom.: 133388

Bravo AF: 0.783

Asia WGS AF: 0.768 AC: 2673 AN: 3478

EpiCase AF: 0.729

EpiControl AF: 0.720

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CPB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.38
DANN	Benign	0.33
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2296642; hg19: chr13-46656669; COSMIC: COSV107983288;