rs3750718

Variant names:

• chr10-100075751-C-A
• rs3750718
• NM_001308.3:c.420+160G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-100075751-C-A
• chr10-100075751-C-T

Variant summary

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

The NM_001308.3(CPN1):​c.420+160G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,228 control chromosomes in the GnomAD database, including 1,826 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 0.11 (1826 hom., cov: 32)
• Consequence: CPN1 NM_001308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 4 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 = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPN1	NM_001308.3	c.420+160G>T		intron_variant	Intron 2 of 8	ENST00000370418.8	NP_001299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPN1	ENST00000370418.8	c.420+160G>T		intron_variant	Intron 2 of 8	1	NM_001308.3	ENSP00000359446.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16779 AN: 152110 Hom.: 1823 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.110 AC: 16793 AN: 152228 Hom.: 1826 Cov.: 32 AF XY: 0.109 AC XY: 8117 AN XY: 74448

African (AFR) AF: 0.274 AC: 11367 AN: 41514

American (AMR) AF: 0.0516 AC: 788 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1389 AN: 5180

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4826

European-Finnish (FIN) AF: 0.0178 AC: 189 AN: 10616

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0318 AC: 2160 AN: 68024

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

Alfa AF: 0.0496 Hom.: 1114

Bravo AF: 0.121

Asia WGS AF: 0.168 AC: 585 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	0.82
DANN	Benign	0.60
PhyloP100		0.21
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: rs3750718; hg19: chr10-101835508;