Variant 19-33302101-TCGCCGCCGC-TCGCCGCCGCCGCCGCCGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_004364.5(CEBPA):c.305_313dupGCGGCGGCG(p.Gly102_Gly104dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000454 in 1,322,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.85

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]

CEBPA links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004364.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPA	NM_004364.5 linkuse as main transcript	c.305_313dupGCGGCGGCG	p.Gly102_Gly104dup	conservative_inframe_insertion	1/1	ENST00000498907.3	NP_004355.2	P49715-1
CEBPA	NM_001287424.2 linkuse as main transcript	c.410_418dupGCGGCGGCG	p.Gly137_Gly139dup	conservative_inframe_insertion	1/1		NP_001274353.1	P49715-4
CEBPA	NM_001287435.2 linkuse as main transcript	c.263_271dupGCGGCGGCG	p.Gly88_Gly90dup	conservative_inframe_insertion	1/1		NP_001274364.1	P49715-2
CEBPA	NM_001285829.2 linkuse as main transcript	c.-53_-45dupGCGGCGGCG		5_prime_UTR_variant	1/1		NP_001272758.1	P49715-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3 linkuse as main transcript	c.305_313dupGCGGCGGCG	p.Gly102_Gly104dup	conservative_inframe_insertion	1/1	6	NM_004364.5	ENSP00000427514.1		P49715-1

Frequencies

GnomAD3 genomes

AF:

0.0000280

AC:

AN:

142988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000759

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000170

AC:

AN:

1179150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

572106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000128

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000280

AC:

AN:

142988

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

69714

show subpopulations

Gnomad4 AFR

AF:

0.0000759

Gnomad4 AMR

AF:

0.0000694

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 2024

In-frame duplication of 3 amino acids in a repetitive region with no known function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Acute myeloid leukemia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2023

This variant, c.305_313dup, results in the insertion of 3 amino acid(s) of the CEBPA protein (p.Gly102_Gly104dup), 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: 937655). 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over