19-33302378-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004364.5(CEBPA):c.37C>A(p.Pro13Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000612 in 1,306,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.37C>A | p.Pro13Thr | missense_variant | Exon 1 of 1 | ENST00000498907.3 | NP_004355.2 | |
CEBPA | NM_001287424.2 | c.142C>A | p.Pro48Thr | missense_variant | Exon 1 of 1 | NP_001274353.1 | ||
CEBPA | NM_001287435.2 | c.-6C>A | 5_prime_UTR_variant | Exon 1 of 1 | NP_001274364.1 | |||
CEBPA | NM_001285829.2 | c.-321C>A | 5_prime_UTR_variant | Exon 1 of 1 | NP_001272758.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151440Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000346 AC: 4AN: 1155348Hom.: 0 Cov.: 32 AF XY: 0.00000180 AC XY: 1AN XY: 556498
GnomAD4 genome AF: 0.0000264 AC: 4AN: 151440Hom.: 0 Cov.: 32 AF XY: 0.0000406 AC XY: 3AN XY: 73980
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.P13T variant (also known as c.37C>A), located in coding exon 1 of the CEBPA gene, results from a C to A substitution at nucleotide position 37. The proline at codon 13 is replaced by threonine, an amino acid with highly similar properties. This variant was identified amongst 22,659 patients with hematological conditions, but germline origin was not confirmed (Hogg G et al. Cancer Genet, 2023 Nov;278-279:38-49). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Acute myeloid leukemia Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1396087). This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 13 of the CEBPA protein (p.Pro13Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at