19-33301983-C-T

Position:

• chr19-33301983-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004364.5(CEBPA):​c.432G>A​(p.Glu144Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,058,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745

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]

ENSG00000267727 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.745 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPA	NM_004364.5	c.432G>A	p.Glu144Glu	synonymous_variant	1/1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001287424.2	c.537G>A	p.Glu179Glu	synonymous_variant	1/1		NP_001274353.1
CEBPA	NM_001287435.2	c.390G>A	p.Glu130Glu	synonymous_variant	1/1		NP_001274364.1
CEBPA	NM_001285829.2	c.75G>A	p.Glu25Glu	synonymous_variant	1/1		NP_001272758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3	c.432G>A	p.Glu144Glu	synonymous_variant	1/1	6	NM_004364.5	ENSP00000427514.1
ENSG00000267727	ENST00000587312.1	n.*43C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1058456 Hom.: 0 Cov.: 33 AF XY: 0.00000198 AC XY: 1 AN XY: 504002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000409

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555742184; hg19: chr19-33792889;