13-46055860-C-A

Variant names:

• chr13-46055860-C-A
• rs1926446
• NM_001872.5:c.1000-11G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001872.5(CPB2):​c.1000-11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,481,948 control chromosomes in the GnomAD database, including 382,523 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 0.76 (44930 hom., cov: 32)
  • Exomes 𝑓: 0.71 (337593 hom.)
• Consequence: CPB2 NM_001872.5 intron
• Scores: Splicing: ADA: 0.00001456
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	NM_001872.5	MANE Select	c.1000-11G>T		intron	N/A	NP_001863.3
	CPB2	NM_001278541.2		c.889-11G>T		intron	N/A	NP_001265470.1
	CPB2-AS1	NR_046226.1		n.118+2895C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.1000-11G>T		intron	N/A	ENSP00000181383.4
	CPB2	ENST00000882332.1		c.1102-11G>T		intron	N/A	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.1048-11G>T		intron	N/A	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116201 AN: 151948 Hom.: 44882 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.723

GnomAD2 exomes AF: 0.735 AC: 170666 AN: 232288 AF XY: 0.726

Gnomad AFR exome AF: 0.865

Gnomad AMR exome AF: 0.787

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.803

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.714

GnomAD4 exome AF: 0.710 AC: 944619 AN: 1329882 Hom.: 337593 Cov.: 18 AF XY: 0.709 AC XY: 472311 AN XY: 666268

African (AFR) AF: 0.861 AC: 25656 AN: 29808

American (AMR) AF: 0.787 AC: 31305 AN: 39788

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 15934 AN: 24656

East Asian (EAS) AF: 0.828 AC: 31449 AN: 37960

South Asian (SAS) AF: 0.684 AC: 52977 AN: 77480

European-Finnish (FIN) AF: 0.806 AC: 40710 AN: 50522

Middle Eastern (MID) AF: 0.638 AC: 3508 AN: 5500

European-Non Finnish (NFE) AF: 0.698 AC: 703644 AN: 1008650

Other (OTH) AF: 0.710 AC: 39436 AN: 55518

GnomAD4 genome AF: 0.765 AC: 116305 AN: 152066 Hom.: 44930 Cov.: 32 AF XY: 0.769 AC XY: 57162 AN XY: 74340

African (AFR) AF: 0.864 AC: 35862 AN: 41518

American (AMR) AF: 0.749 AC: 11446 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2274 AN: 3464

East Asian (EAS) AF: 0.803 AC: 4158 AN: 5178

South Asian (SAS) AF: 0.702 AC: 3383 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8545 AN: 10544

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48324 AN: 67950

Other (OTH) AF: 0.724 AC: 1530 AN: 2112

Alfa AF: 0.737 Hom.: 15489

Bravo AF: 0.764

Asia WGS AF: 0.763 AC: 2644 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.021
DANN	Benign	0.58
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0020
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: rs1926446; hg19: chr13-46629995;