NM_001872.5:c.663A>G

Variant names:

• chr13-46067346-T-C
• rs7337140
• NM_001872.5:c.663A>G

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.663A>G​(p.Pro221Pro) 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 1,583,384 control chromosomes in the GnomAD database, including 448,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.79 (47659 hom., cov: 32)
  • Exomes 𝑓: 0.75 (400543 hom.)
• Consequence: CPB2 NM_001872.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.66
• Publications: 23 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=-0.93).
• BP6: Variant 13-46067346-T-C is Benign according to our data. Variant chr13-46067346-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060410.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 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.663A>G	p.Pro221Pro	synonymous	Exon 7 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.592-2605A>G		intron	N/A	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.118+14381T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.663A>G	p.Pro221Pro	synonymous	Exon 7 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.765A>G	p.Pro255Pro	synonymous	Exon 7 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.711A>G	p.Pro237Pro	synonymous	Exon 7 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119867 AN: 152020 Hom.: 47613 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.751

GnomAD2 exomes AF: 0.765 AC: 191960 AN: 250768 AF XY: 0.757

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.828

Gnomad FIN exome AF: 0.816

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.746 AC: 1067777 AN: 1431246 Hom.: 400543 Cov.: 29 AF XY: 0.744 AC XY: 531151 AN XY: 713736

African (AFR) AF: 0.879 AC: 28865 AN: 32830

American (AMR) AF: 0.813 AC: 36259 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18174 AN: 25898

East Asian (EAS) AF: 0.846 AC: 33352 AN: 39446

South Asian (SAS) AF: 0.710 AC: 60736 AN: 85534

European-Finnish (FIN) AF: 0.814 AC: 43431 AN: 53352

Middle Eastern (MID) AF: 0.684 AC: 3904 AN: 5704

European-Non Finnish (NFE) AF: 0.737 AC: 799010 AN: 1084574

Other (OTH) AF: 0.743 AC: 44046 AN: 59298

GnomAD4 genome AF: 0.789 AC: 119969 AN: 152138 Hom.: 47659 Cov.: 32 AF XY: 0.790 AC XY: 58795 AN XY: 74386

African (AFR) AF: 0.878 AC: 36431 AN: 41506

American (AMR) AF: 0.776 AC: 11856 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2449 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4250 AN: 5182

South Asian (SAS) AF: 0.715 AC: 3445 AN: 4816

European-Finnish (FIN) AF: 0.814 AC: 8605 AN: 10570

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50544 AN: 68002

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.750 Hom.: 69565

Bravo AF: 0.789

Asia WGS AF: 0.775 AC: 2693 AN: 3476

ClinVar

ClinVar submissions

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	-0.93
CADD	Benign	0.025
DANN	Benign	0.45
PhyloP100		-1.7
Mutation Taster		=99/1	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: rs7337140; hg19: chr13-46641481; COSMIC: COSV51672366;