rs1555742103
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004364.5(CEBPA):c.576_577insTACCCG(p.Pro192_His193insTyrPro) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P192P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
CEBPA
NM_004364.5 inframe_insertion
NM_004364.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.427
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.576_577insTACCCG | p.Pro192_His193insTyrPro | inframe_insertion | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001285829.2 | c.219_220insTACCCG | p.Pro73_His74insTyrPro | inframe_insertion | 1/1 | ||
CEBPA | NM_001287424.2 | c.681_682insTACCCG | p.Pro227_His228insTyrPro | inframe_insertion | 1/1 | ||
CEBPA | NM_001287435.2 | c.534_535insTACCCG | p.Pro178_His179insTyrPro | inframe_insertion | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.576_577insTACCCG | p.Pro192_His193insTyrPro | inframe_insertion | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.385_386insACGGGT | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 10, 2017 | - - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with CEBPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 434687). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.576_577insTACCCG, results in the insertion of 2 amino acid(s) to the CEBPA protein (p.Pro192_His193insTyrPro), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at