NM_004364.5:c.68dupC
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_004364.5(CEBPA):c.68dupC(p.His24AlafsTer84) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,195,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Consequence
CEBPA
NM_004364.5 frameshift
NM_004364.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.177
Genes affected
CEBPA (HGNC:1833): (CCAAT enhancer binding protein alpha) This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.937 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-33302346-C-CG is Pathogenic according to our data. Variant chr19-33302346-C-CG is described in ClinVar as [Pathogenic]. Clinvar id is 21401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CEBPA | NM_004364.5 | c.68dupC | p.His24AlafsTer84 | frameshift_variant | Exon 1 of 1 | ENST00000498907.3 | NP_004355.2 | |
| CEBPA | NM_001287424.2 | c.173dupC | p.His59AlafsTer84 | frameshift_variant | Exon 1 of 1 | NP_001274353.1 | ||
| CEBPA | NM_001287435.2 | c.26dupC | p.His10AlafsTer84 | frameshift_variant | Exon 1 of 1 | NP_001274364.1 | ||
| CEBPA | NM_001285829.2 | c.-290dupC | 5_prime_UTR_variant | Exon 1 of 1 | NP_001272758.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000335 AC: 4AN: 1195068Hom.: 0 Cov.: 32 AF XY: 0.00000344 AC XY: 2AN XY: 581784
GnomAD4 exome
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32
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Acute myeloid leukemia Pathogenic:1Other:1
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GeneReviews
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
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Genomic Diagnostics Laboratory, National Institute of Medical Genomics
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The variant was detected in bone marrow from patients, but it was not confirmed in the matched -
not provided Pathogenic:1
Dec 15, 2017
Clinical Genetics and Genomics, Karolinska University Hospital
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at