10-100045685-C-T

Variant names:

• chr10-100045685-C-T
• rs11599750
• NM_001308.3:c.1230+3073G>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.1230+3073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,044 control chromosomes in the GnomAD database, including 12,292 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 0.39 (12292 hom., cov: 33)
• Consequence: CPN1 NM_001308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 53 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPN1	NM_001308.3	c.1230+3073G>A		intron_variant	Intron 8 of 8	ENST00000370418.8	NP_001299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPN1	ENST00000370418.8	c.1230+3073G>A		intron_variant	Intron 8 of 8	1	NM_001308.3	ENSP00000359446.3

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59847 AN: 151926 Hom.: 12251 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.394 AC: 59942 AN: 152044 Hom.: 12292 Cov.: 33 AF XY: 0.386 AC XY: 28716 AN XY: 74332

African (AFR) AF: 0.458 AC: 18980 AN: 41432

American (AMR) AF: 0.435 AC: 6647 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3472

East Asian (EAS) AF: 0.177 AC: 918 AN: 5182

South Asian (SAS) AF: 0.176 AC: 846 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 3016 AN: 10582

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26912 AN: 67970

Other (OTH) AF: 0.420 AC: 887 AN: 2114

Alfa AF: 0.391 Hom.: 52784

Bravo AF: 0.413

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.57
PhyloP100		0.45
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: rs11599750; hg19: chr10-101805442;