NM_004364.5:c.576_577insTACCCG

Variant names:

• chr19-33301838-G-GCGGGTA
• rs1555742103
• NM_004364.5:c.576_577insTACCCG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_004364.5(CEBPA):​c.576_577insTACCCG​(p.Pro192_His193insTyrPro) 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P192P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEBPA NM_004364.5 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.427
• Publications: 0 publications found

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:):

CEBPA-DT (HGNC:25710): (CEBPA divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_004364.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	NM_004364.5	MANE Select	c.576_577insTACCCG	p.Pro192_His193insTyrPro	conservative_inframe_insertion	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.681_682insTACCCG	p.Pro227_His228insTyrPro	conservative_inframe_insertion	Exon 1 of 1	NP_001274353.1	P49715-4
	CEBPA	NM_001287435.2		c.534_535insTACCCG	p.Pro178_His179insTyrPro	conservative_inframe_insertion	Exon 1 of 1	NP_001274364.1	P49715-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.576_577insTACCCG	p.Pro192_His193insTyrPro	conservative_inframe_insertion	Exon 1 of 1	ENSP00000427514.1	P49715-1
	ENSG00000267727	ENST00000587312.1	TSL:3	n.385_386insACGGGT		non_coding_transcript_exon	Exon 2 of 2
	CEBPA-DT	ENST00000718467.1		n.46+44_46+45insACGGGT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Acute myeloid leukemia (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1555742103; hg19: chr19-33792744;