chr13-46067331-A-G

Variant names:

• chr13-46067331-A-G
• rs9316179
• NM_001872.5:c.678T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001872.5(CPB2):​c.678T>C​(p.Asp226Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,553,388 control chromosomes in the GnomAD database, including 79,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9200 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70087 hom.)
• Consequence: CPB2 NM_001872.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.967
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 13-46067331-A-G is Benign according to our data. Variant chr13-46067331-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059117.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.967 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 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.678T>C	p.Asp226Asp	synonymous	Exon 7 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.592-2590T>C		intron	N/A	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.118+14366A>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.678T>C	p.Asp226Asp	synonymous	Exon 7 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.780T>C	p.Asp260Asp	synonymous	Exon 7 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.726T>C	p.Asp242Asp	synonymous	Exon 7 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52177 AN: 151950 Hom.: 9194 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.348

GnomAD2 exomes AF: 0.313 AC: 78482 AN: 250670 AF XY: 0.308

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.261

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.312 AC: 436738 AN: 1401320 Hom.: 70087 Cov.: 25 AF XY: 0.310 AC XY: 217019 AN XY: 700450

African (AFR) AF: 0.384 AC: 12285 AN: 31990

American (AMR) AF: 0.295 AC: 13174 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8931 AN: 25724

East Asian (EAS) AF: 0.257 AC: 10108 AN: 39298

South Asian (SAS) AF: 0.214 AC: 18177 AN: 85082

European-Finnish (FIN) AF: 0.394 AC: 21006 AN: 53296

Middle Eastern (MID) AF: 0.314 AC: 1777 AN: 5668

European-Non Finnish (NFE) AF: 0.315 AC: 332945 AN: 1057328

Other (OTH) AF: 0.314 AC: 18335 AN: 58350

GnomAD4 genome AF: 0.343 AC: 52215 AN: 152068 Hom.: 9200 Cov.: 32 AF XY: 0.344 AC XY: 25561 AN XY: 74356

African (AFR) AF: 0.391 AC: 16196 AN: 41470

American (AMR) AF: 0.325 AC: 4962 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1335 AN: 5180

South Asian (SAS) AF: 0.206 AC: 995 AN: 4824

European-Finnish (FIN) AF: 0.398 AC: 4213 AN: 10580

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22218 AN: 67960

Other (OTH) AF: 0.347 AC: 732 AN: 2108

Alfa AF: 0.327 Hom.: 12603

Bravo AF: 0.338

Asia WGS AF: 0.262 AC: 912 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CPB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.0
DANN	Benign	0.56
PhyloP100		0.97
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: rs9316179; hg19: chr13-46641466; COSMIC: COSV51674341;