rs1408671093
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004364.5(CEBPA):c.421G>T(p.Gly141Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,191,248 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G141R) has been classified as Likely benign.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.421G>T | p.Gly141Cys | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.526G>T | p.Gly176Cys | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.379G>T | p.Gly127Cys | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.64G>T | p.Gly22Cys | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.421G>T | p.Gly141Cys | missense_variant | 1/1 | NM_004364.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000337 AC: 5AN: 148458Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000192 AC: 20AN: 1042682Hom.: 0 Cov.: 33 AF XY: 0.0000182 AC XY: 9AN XY: 494242
GnomAD4 genome ? AF: 0.0000337 AC: 5AN: 148566Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 2AN XY: 72474
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 141 of the CEBPA protein (p.Gly141Cys). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 456686). 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. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 09, 2023 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at