chr10-100076007-C-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001308.3(CPN1):c.324G>C(p.Arg108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,614,062 control chromosomes in the GnomAD database, including 636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.035 ( 314 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 322 hom. )
Consequence
CPN1
NM_001308.3 synonymous
NM_001308.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.970
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-100076007-C-G is Benign according to our data. Variant chr10-100076007-C-G is described in ClinVar as [Benign]. Clinvar id is 3038291.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.97 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPN1 | NM_001308.3 | c.324G>C | p.Arg108= | synonymous_variant | 2/9 | ENST00000370418.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPN1 | ENST00000370418.8 | c.324G>C | p.Arg108= | synonymous_variant | 2/9 | 1 | NM_001308.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0349 AC: 5308AN: 152066Hom.: 308 Cov.: 32
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GnomAD3 exomes AF: 0.00922 AC: 2318AN: 251464Hom.: 123 AF XY: 0.00678 AC XY: 922AN XY: 135910
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GnomAD4 exome AF: 0.00404 AC: 5900AN: 1461878Hom.: 322 Cov.: 31 AF XY: 0.00348 AC XY: 2529AN XY: 727242
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GnomAD4 genome ? AF: 0.0350 AC: 5332AN: 152184Hom.: 314 Cov.: 32 AF XY: 0.0345 AC XY: 2565AN XY: 74390
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CPN1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 28, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at