chr10-100065200-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001308.3(CPN1):c.747G>A(p.Lys249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,268 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.011 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 20 hom. )
Consequence
CPN1
NM_001308.3 synonymous
NM_001308.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
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=-0.57).
BP6
?
Variant 10-100065200-C-T is Benign according to our data. Variant chr10-100065200-C-T is described in ClinVar as [Benign]. Clinvar id is 780887.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.07 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1669/152310) while in subpopulation AFR AF= 0.0384 (1598/41578). AF 95% confidence interval is 0.0369. There are 26 homozygotes in gnomad4. There are 771 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPN1 | NM_001308.3 | c.747G>A | p.Lys249= | synonymous_variant | 4/9 | ENST00000370418.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPN1 | ENST00000370418.8 | c.747G>A | p.Lys249= | synonymous_variant | 4/9 | 1 | NM_001308.3 | P1 | |
CPN1 | ENST00000441382.1 | c.138G>A | p.Lys46= | synonymous_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0109 AC: 1666AN: 152192Hom.: 26 Cov.: 32
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GnomAD3 exomes AF: 0.00295 AC: 738AN: 250070Hom.: 15 AF XY: 0.00219 AC XY: 296AN XY: 135302
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GnomAD4 exome AF: 0.00100 AC: 1463AN: 1460958Hom.: 20 Cov.: 31 AF XY: 0.000812 AC XY: 590AN XY: 726620
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GnomAD4 genome ? AF: 0.0110 AC: 1669AN: 152310Hom.: 26 Cov.: 32 AF XY: 0.0104 AC XY: 771AN XY: 74492
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at