rs1555741967

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5

The NM_004364.5(CEBPA):​c.925_951dupGAGACGCAGCAGAAGGTGCTGGAGCTG​(p.Leu317_Thr318insGluThrGlnGlnLysValLeuGluLeu) variant causes a conservative 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

CEBPA
NM_004364.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.40
Variant links:
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 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004364.5.
PP5
Variant 19-33301463-T-TCAGCTCCAGCACCTTCTGCTGCGTCTC is Pathogenic according to our data. Variant chr19-33301463-T-TCAGCTCCAGCACCTTCTGCTGCGTCTC is described in ClinVar as [Pathogenic]. Clinvar id is 17570.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CEBPANM_004364.5 linkc.925_951dupGAGACGCAGCAGAAGGTGCTGGAGCTG p.Leu317_Thr318insGluThrGlnGlnLysValLeuGluLeu conservative_inframe_insertion 1/1 ENST00000498907.3 NP_004355.2 P49715-1
CEBPANM_001287424.2 linkc.1030_1056dupGAGACGCAGCAGAAGGTGCTGGAGCTG p.Leu352_Thr353insGluThrGlnGlnLysValLeuGluLeu conservative_inframe_insertion 1/1 NP_001274353.1 P49715-4
CEBPANM_001287435.2 linkc.883_909dupGAGACGCAGCAGAAGGTGCTGGAGCTG p.Leu303_Thr304insGluThrGlnGlnLysValLeuGluLeu conservative_inframe_insertion 1/1 NP_001274364.1 P49715-2
CEBPANM_001285829.2 linkc.568_594dupGAGACGCAGCAGAAGGTGCTGGAGCTG p.Leu198_Thr199insGluThrGlnGlnLysValLeuGluLeu conservative_inframe_insertion 1/1 NP_001272758.1 P49715-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CEBPAENST00000498907.3 linkc.925_951dupGAGACGCAGCAGAAGGTGCTGGAGCTG p.Leu317_Thr318insGluThrGlnGlnLysValLeuGluLeu conservative_inframe_insertion 1/16 NM_004364.5 ENSP00000427514.1 P49715-1
ENSG00000267727ENST00000587312.1 linkn.188_214dupGCTCCAGCACCTTCTGCTGCGTCTCCA non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Acute myeloid leukemia Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555741967; hg19: chr19-33792369; API