rs940

Positions:

• chr13-46053345-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPB2	NM_001872.5	c.*269G>C		3_prime_UTR_variant	11/11	ENST00000181383.10
CPB2-AS1	NR_046226.1	n.118+380C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPB2	ENST00000181383.10	c.*269G>C		3_prime_UTR_variant	11/11	1	NM_001872.5	P1
CPB2-AS1	ENST00000663159.1	n.469+380C>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.793

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.740

Gnomad4 OTH exome AF: 0.747

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

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.750

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.5
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs940; hg19: chr13-46627480;