10-100068504-C-T

Variant names:

• chr10-100068504-C-T
• rs61871700
• NM_001308.3:c.576+1210G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308.3(CPN1):​c.576+1210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,542 control chromosomes in the GnomAD database, including 8,251 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 0.29 (8251 hom., cov: 30)
• Consequence: CPN1 NM_001308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 publications found

Genes affected

CPN1 (HGNC:2312): (carboxypeptidase N subunit 1) Carboxypeptidase N is a plasma metallo-protease that cleaves basic amino acids from the C terminal of peptides and proteins. The enzyme is important in the regulation of peptides like kinins and anaphylatoxins, and has also been known as kininase-1 and anaphylatoxin inactivator. This enzyme is a tetramer comprised of two identical regulatory subunits and two identical catalytic subunits; this gene encodes the catalytic subunit. Mutations in this gene can be associated with angioedema or chronic urticaria resulting from carboxypeptidase N deficiency. [provided by RefSeq, Jul 2008]

CPN1 Gene-Disease associations (from GenCC):

• carboxypeptidase N deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308.3. 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
	CPN1	NM_001308.3	MANE Select	c.576+1210G>A		intron	N/A	NP_001299.1	P15169

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPN1	ENST00000370418.8	TSL:1 MANE Select	c.576+1210G>A		intron	N/A	ENSP00000359446.3	P15169
	CPN1	ENST00000877015.1		c.576+1210G>A		intron	N/A	ENSP00000547074.1
	CPN1	ENST00000877014.1		c.576+1210G>A		intron	N/A	ENSP00000547073.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44637 AN: 151420 Hom.: 8251 Cov.: 30

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.295 AC: 44644 AN: 151542 Hom.: 8251 Cov.: 30 AF XY: 0.300 AC XY: 22208 AN XY: 74012

African (AFR) AF: 0.0691 AC: 2860 AN: 41376

American (AMR) AF: 0.376 AC: 5733 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.462 AC: 2338 AN: 5056

South Asian (SAS) AF: 0.349 AC: 1670 AN: 4790

European-Finnish (FIN) AF: 0.428 AC: 4479 AN: 10476

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25466 AN: 67832

Other (OTH) AF: 0.292 AC: 617 AN: 2110

Alfa AF: 0.287 Hom.: 1418

Bravo AF: 0.280

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-1.4
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: rs61871700; hg19: chr10-101828261;