rs558462037
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_004364.5(CEBPA):c.184A>G(p.Ile62Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,495,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I62M) has been classified as Uncertain significance.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.184A>G | p.Ile62Val | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.289A>G | p.Ile97Val | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.142A>G | p.Ile48Val | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.-174A>G | 5_prime_UTR_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.184A>G | p.Ile62Val | missense_variant | 1/1 | NM_004364.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151488Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000551 AC: 74AN: 1344108Hom.: 0 Cov.: 33 AF XY: 0.0000483 AC XY: 32AN XY: 662872
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151600Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74082
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 62 of the CEBPA protein (p.Ile62Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 578986). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEBPA protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at