chr13-46078860-A-G

Variant names:

• chr13-46078860-A-G
• rs11574989
• NM_001872.5:c.426T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001872.5(CPB2):​c.426T>C​(p.Asp142Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000971 in 1,612,232 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (9 hom.)
• Consequence: CPB2 NM_001872.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.177
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-46078860-A-G is Benign according to our data. Variant chr13-46078860-A-G is described in ClinVar as Benign. ClinVar VariationId is 710029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.177 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00515 (785/152314) while in subpopulation AFR AF = 0.0175 (727/41570). AF 95% confidence interval is 0.0164. There are 9 homozygotes in GnomAd4. There are 389 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.426T>C	p.Asp142Asp	synonymous	Exon 5 of 11	NP_001863.3	Q96IY4-1
	CPB2	NM_001278541.2		c.426T>C	p.Asp142Asp	synonymous	Exon 5 of 10	NP_001265470.1	A0A087WSY5
	CPB2-AS1	NR_046226.1		n.119-15993A>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.426T>C	p.Asp142Asp	synonymous	Exon 5 of 11	ENSP00000181383.4	Q96IY4-1
	CPB2	ENST00000882332.1		c.528T>C	p.Asp176Asp	synonymous	Exon 5 of 11	ENSP00000552391.1
	CPB2	ENST00000882315.1		c.474T>C	p.Asp158Asp	synonymous	Exon 5 of 11	ENSP00000552374.1

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 777 AN: 152196 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00141 AC: 355 AN: 251004 AF XY: 0.000995

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.000927

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000534 AC: 780 AN: 1459918 Hom.: 9 Cov.: 28 AF XY: 0.000446 AC XY: 324 AN XY: 726384

African (AFR) AF: 0.0161 AC: 537 AN: 33428

American (AMR) AF: 0.00136 AC: 61 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000696 AC: 60 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1110544

Other (OTH) AF: 0.00182 AC: 110 AN: 60354

GnomAD4 genome AF: 0.00515 AC: 785 AN: 152314 Hom.: 9 Cov.: 32 AF XY: 0.00522 AC XY: 389 AN XY: 74478

African (AFR) AF: 0.0175 AC: 727 AN: 41570

American (AMR) AF: 0.00262 AC: 40 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00251 Hom.: 1

Bravo AF: 0.00619

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.33
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs11574989; hg19: chr13-46652995;