rs1926446

Positions:

• chr13-46055860-C-A
• chr13-46055860-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.1000-11G>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001456
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPB2	NM_001872.5	c.1000-11G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000181383.10	NP_001863.3
CPB2-AS1	NR_046226.1	n.118+2895C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10	c.1000-11G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001872.5	ENSP00000181383	P1
CPB2-AS1	ENST00000663159.1	n.469+2895C>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.735 AC: 170666 AN: 232288 Hom.: 63199 AF XY: 0.726 AC XY: 91568 AN XY: 126150

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 SAS exome AF: 0.681

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

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.710

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

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.724

Alfa AF: 0.734 Hom.: 9498

Bravo AF: 0.764

Asia WGS AF: 0.763 AC: 2644 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.021
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1926446; hg19: chr13-46629995;