chr19-33302241-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004364.5(CEBPA):āc.174C>Gā(p.His58Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 1,491,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. H58H) has been classified as Likely benign.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.174C>G | p.His58Gln | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.279C>G | p.His93Gln | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.132C>G | p.His44Gln | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.-184C>G | 5_prime_UTR_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.174C>G | p.His58Gln | missense_variant | 1/1 | NM_004364.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151630Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000149 AC: 2AN: 1339438Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 660618
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151630Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74062
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1366703). This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 58 of the CEBPA protein (p.His58Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at