rs940

Variant names:

• chr13-46053345-C-G
• rs940
• NM_001872.5:c.*269G>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.*269G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 306,836 control chromosomes in the GnomAD database, including 92,060 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 0.79 (47457 hom., cov: 31)
  • Exomes 𝑓: 0.76 (44603 hom.)
• Consequence: CPB2 NM_001872.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 30 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 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.*269G>C		3_prime_UTR	Exon 11 of 11	NP_001863.3
	CPB2	NM_001278541.2		c.*269G>C		3_prime_UTR	Exon 10 of 10	NP_001265470.1
	CPB2-AS1	NR_046226.1		n.118+380C>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.*269G>C		3_prime_UTR	Exon 11 of 11	ENSP00000181383.4
	CPB2	ENST00000882332.1		c.*269G>C		3_prime_UTR	Exon 11 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.*269G>C		3_prime_UTR	Exon 11 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119601 AN: 151968 Hom.: 47411 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.749

GnomAD4 exome AF: 0.756 AC: 117042 AN: 154750 Hom.: 44603 Cov.: 4 AF XY: 0.752 AC XY: 60024 AN XY: 79832

African (AFR) AF: 0.876 AC: 4904 AN: 5598

American (AMR) AF: 0.793 AC: 5134 AN: 6472

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 3871 AN: 5512

East Asian (EAS) AF: 0.838 AC: 10208 AN: 12176

South Asian (SAS) AF: 0.703 AC: 5026 AN: 7154

European-Finnish (FIN) AF: 0.832 AC: 5902 AN: 7096

Middle Eastern (MID) AF: 0.662 AC: 498 AN: 752

European-Non Finnish (NFE) AF: 0.740 AC: 74425 AN: 100516

Other (OTH) AF: 0.747 AC: 7074 AN: 9474

GnomAD4 genome AF: 0.787 AC: 119702 AN: 152086 Hom.: 47457 Cov.: 31 AF XY: 0.789 AC XY: 58669 AN XY: 74324

African (AFR) AF: 0.870 AC: 36093 AN: 41486

American (AMR) AF: 0.774 AC: 11825 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2454 AN: 3470

East Asian (EAS) AF: 0.804 AC: 4159 AN: 5176

South Asian (SAS) AF: 0.708 AC: 3406 AN: 4808

European-Finnish (FIN) AF: 0.828 AC: 8745 AN: 10560

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50646 AN: 67992

Other (OTH) AF: 0.750 AC: 1586 AN: 2116

Alfa AF: 0.786 Hom.: 5881

Bravo AF: 0.786

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.5
DANN	Benign	0.88
PhyloP100		0.010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs940; hg19: chr13-46627480;