chr4-165467673-C-CT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001873.4(CPE):c.505-3dup 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 0.023 in 1,195,554 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 24 hom., cov: 32)
Exomes 𝑓: 0.025 ( 0 hom. )
Consequence
CPE
NM_001873.4 splice_polypyrimidine_tract, intron
NM_001873.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.381
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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 4-165467673-C-CT is Benign according to our data. Variant chr4-165467673-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1645773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPE | NM_001873.4 | c.505-3dup | splice_polypyrimidine_tract_variant, intron_variant | ENST00000402744.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPE | ENST00000402744.9 | c.505-3dup | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001873.4 | P1 | |||
CPE | ENST00000431967.5 | c.169-3dup | splice_polypyrimidine_tract_variant, intron_variant | 4 | |||||
CPE | ENST00000511992.1 | c.169-3dup | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
CPE | ENST00000513982.5 | c.169-3dup | splice_polypyrimidine_tract_variant, intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0113 AC: 1630AN: 144812Hom.: 24 Cov.: 32
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GnomAD4 exome AF: 0.0246 AC: 25887AN: 1050712Hom.: 0 Cov.: 0 AF XY: 0.0248 AC XY: 13016AN XY: 524790
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GnomAD4 genome ? AF: 0.0113 AC: 1631AN: 144842Hom.: 24 Cov.: 32 AF XY: 0.0111 AC XY: 784AN XY: 70426
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
BDV syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 14, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at