chr13-46093976-A-G

Variant names:

• chr13-46093976-A-G
• rs2146882
• NM_001872.5:c.75-6156T>C

Variant summary

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

The NM_001872.5(CPB2):​c.75-6156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,060 control chromosomes in the GnomAD database, including 41,303 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 0.74 (41303 hom., cov: 31)
• Consequence: CPB2 NM_001872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 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.75-6156T>C		intron	N/A	NP_001863.3
	CPB2	NM_001278541.2		c.75-6156T>C		intron	N/A	NP_001265470.1
	CPB2-AS1	NR_046226.1		n.119-877A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPB2	ENST00000181383.10	TSL:1 MANE Select	c.75-6156T>C		intron	N/A	ENSP00000181383.4
	CPB2	ENST00000439329.5	TSL:5	c.75-6156T>C		intron	N/A	ENSP00000400714.3
	CPB2	ENST00000674625.1		c.75-6156T>C		intron	N/A	ENSP00000502808.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111700 AN: 151942 Hom.: 41274 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.735 AC: 111780 AN: 152060 Hom.: 41303 Cov.: 31 AF XY: 0.739 AC XY: 54920 AN XY: 74300

African (AFR) AF: 0.684 AC: 28358 AN: 41450

American (AMR) AF: 0.759 AC: 11607 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2425 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4208 AN: 5166

South Asian (SAS) AF: 0.718 AC: 3454 AN: 4812

European-Finnish (FIN) AF: 0.815 AC: 8617 AN: 10578

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50811 AN: 67976

Other (OTH) AF: 0.712 AC: 1502 AN: 2110

Alfa AF: 0.747 Hom.: 9194

Bravo AF: 0.728

Asia WGS AF: 0.761 AC: 2643 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		0.018
Mutation Taster		=100/0	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: rs2146882; hg19: chr13-46668111; COSMIC: COSV51677653;