rs17844078

chr13-46070689-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001872.5(CPB2):c.591+3184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,324 control chromosomes in the GnomAD database, including 82 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 0.027 (82 hom., cov: 32)
• Consequence: CPB2 NM_001872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.027 (4114/152324) while in subpopulation NFE AF= 0.042 (2857/68024). AF 95% confidence interval is 0.0407. There are 82 homozygotes in gnomad4. There are 1926 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPB2	NM_001872.5	c.591+3184T>C		intron_variant		ENST00000181383.10
CPB2-AS1	NR_046226.1	n.118+17724A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPB2	ENST00000181383.10	c.591+3184T>C		intron_variant		1	NM_001872.5	P1
CPB2-AS1	ENST00000663159.1	n.469+17724A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4115 AN: 152206 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00866

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0270 AC: 4114 AN: 152324 Hom.: 82 Cov.: 32 AF XY: 0.0259 AC XY: 1926 AN XY: 74492

Gnomad4 AFR AF: 0.00864

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0329 Hom.: 15

Bravo AF: 0.0284

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.76

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: rs17844078; hg19: chr13-46644824;