chr4-165467673-CTT-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1
The NM_001873.4(CPE):c.505-4_505-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,277,438 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000090 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 1 hom. )
Consequence
CPE
NM_001873.4 splice_polypyrimidine_tract, intron
NM_001873.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.40
Genes affected
CPE (HGNC:2303): (carboxypeptidase E) This gene encodes a member of the M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature peptidase. This peripheral membrane protein cleaves C-terminal amino acid residues and is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. This protein may also function independently of its peptidase activity, as a neurotrophic factor that promotes neuronal survival, and as a sorting receptor that binds to regulated secretory pathway proteins, including prohormones. Mutations in this gene are implicated in type 2 diabetes. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 4-165467673-CTT-C is Benign according to our data. Variant chr4-165467673-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044911.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000897 (13/144852) while in subpopulation EAS AF= 0.0012 (6/4992). AF 95% confidence interval is 0.000523. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPE | NM_001873.4 | c.505-4_505-3del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000402744.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPE | ENST00000402744.9 | c.505-4_505-3del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001873.4 | P1 | |||
CPE | ENST00000431967.5 | c.169-4_169-3del | splice_polypyrimidine_tract_variant, intron_variant | 4 | |||||
CPE | ENST00000511992.1 | c.169-4_169-3del | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
CPE | ENST00000513982.5 | c.169-4_169-3del | splice_polypyrimidine_tract_variant, intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000898 AC: 13AN: 144824Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00109 AC: 1232AN: 1132586Hom.: 1 AF XY: 0.00113 AC XY: 636AN XY: 563442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CPE-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 07, 2022 | This variant is classified as likely 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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at