chr13-46064691-G-A

Variant names:

• chr13-46064691-G-A
• rs2277440
• NM_001872.5:c.753C>T

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.753C>T​(p.Ile251Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,613,616 control chromosomes in the GnomAD database, including 7,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.094 (869 hom., cov: 32)
  • Exomes 𝑓: 0.079 (6179 hom.)
• Consequence: CPB2 NM_001872.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.18
• Publications: 13 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=-0.71).
• BP6: Variant 13-46064691-G-A is Benign according to our data. Variant chr13-46064691-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059439.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 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.753C>T	p.Ile251Ile	synonymous	Exon 8 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.642C>T	p.Ile214Ile	synonymous	Exon 7 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.118+11726G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.753C>T	p.Ile251Ile	synonymous	Exon 8 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.855C>T	p.Ile285Ile	synonymous	Exon 8 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.801C>T	p.Ile267Ile	synonymous	Exon 8 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14390 AN: 152086 Hom.: 871 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.109 AC: 27302 AN: 251388 AF XY: 0.103

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.0695

Gnomad EAS exome AF: 0.304

Gnomad FIN exome AF: 0.0424

Gnomad NFE exome AF: 0.0639

Gnomad OTH exome AF: 0.0949

GnomAD4 exome AF: 0.0790 AC: 115472 AN: 1461412 Hom.: 6179 Cov.: 31 AF XY: 0.0791 AC XY: 57521 AN XY: 727036

African (AFR) AF: 0.114 AC: 3819 AN: 33458

American (AMR) AF: 0.192 AC: 8563 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 1829 AN: 26132

East Asian (EAS) AF: 0.288 AC: 11435 AN: 39668

South Asian (SAS) AF: 0.114 AC: 9841 AN: 86212

European-Finnish (FIN) AF: 0.0416 AC: 2223 AN: 53398

Middle Eastern (MID) AF: 0.0966 AC: 557 AN: 5768

European-Non Finnish (NFE) AF: 0.0645 AC: 71679 AN: 1111698

Other (OTH) AF: 0.0915 AC: 5526 AN: 60372

GnomAD4 genome AF: 0.0945 AC: 14381 AN: 152204 Hom.: 869 Cov.: 32 AF XY: 0.0945 AC XY: 7029 AN XY: 74412

African (AFR) AF: 0.118 AC: 4891 AN: 41504

American (AMR) AF: 0.136 AC: 2077 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1478 AN: 5170

South Asian (SAS) AF: 0.122 AC: 591 AN: 4826

European-Finnish (FIN) AF: 0.0422 AC: 447 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0645 AC: 4386 AN: 68016

Other (OTH) AF: 0.0985 AC: 208 AN: 2112

Alfa AF: 0.0784 Hom.: 1049

Bravo AF: 0.107

Asia WGS AF: 0.180 AC: 623 AN: 3478

EpiCase AF: 0.0651

EpiControl AF: 0.0679

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	-0.71
CADD	Benign	0.85
DANN	Benign	0.65
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2277440; hg19: chr13-46638826; COSMIC: COSV51672963;