rs762459325

Positions:

• chr19-33301825-GGCGGGTGCGGGT-G
• chr19-33301825-GGCGGGTGCGGGT-GGCGGGT
• chr19-33301825-GGCGGGTGCGGGT-GGCGGGTGCGGGTGCGGGT
• chr19-33301825-GGCGGGTGCGGGT-GGCGGGTGCGGGTGCGGGTGCGGGT
• chr19-33301825-GGCGGGTGCGGGT-GGCGGGTGCGGGTGCGGGTGCGGGTGCGGGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004364.5(CEBPA):​c.578_589del​(p.His193_Pro196del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 1,115,488 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: CEBPA NM_004364.5 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPA	NM_004364.5	c.578_589del	p.His193_Pro196del	inframe_deletion	1/1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001285829.2	c.221_232del	p.His74_Pro77del	inframe_deletion	1/1		NP_001272758.1
CEBPA	NM_001287424.2	c.683_694del	p.His228_Pro231del	inframe_deletion	1/1		NP_001274353.1
CEBPA	NM_001287435.2	c.536_547del	p.His179_Pro182del	inframe_deletion	1/1		NP_001274364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3	c.578_589del	p.His193_Pro196del	inframe_deletion	1/1		NM_004364.5	ENSP00000427514	P1
	ENST00000587312.1	n.377_388del		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000896 AC: 10 AN: 1115488 Hom.: 0 AF XY: 0.0000111 AC XY: 6 AN XY: 541524

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acute myeloid leukemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 05, 2023

This variant, c.578_589del, results in the deletion of 4 amino acid(s) of the CEBPA protein (p.His193_Pro196del), but otherwise preserves the integrity of the reading frame. 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: 526815). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs762459325; hg19: chr19-33792731;