rs780345232

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_004364.5(CEBPA):c.305_313delGCGGCGGCG(p.Gly102_Gly104del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000227 in 1,322,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G102G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 3.82

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:

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

CEBPA-DT links:

ENSG00000267727 (HGNC:):

ENSG00000267727 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004364.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5 link	c.305_313delGCGGCGGCG	p.Gly102_Gly104del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000498907.3	NP_004355.2	P49715-1
CEBPA	NM_001287424.2 link	c.410_418delGCGGCGGCG	p.Gly137_Gly139del	disruptive_inframe_deletion	Exon 1 of 1		NP_001274353.1	P49715-4
CEBPA	NM_001287435.2 link	c.263_271delGCGGCGGCG	p.Gly88_Gly90del	disruptive_inframe_deletion	Exon 1 of 1		NP_001274364.1	P49715-2
CEBPA	NM_001285829.2 link	c.-53_-45delGCGGCGGCG		5_prime_UTR_variant	Exon 1 of 1		NP_001272758.1	P49715-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEBPA	ENST00000498907.3 link	c.305_313delGCGGCGGCG	p.Gly102_Gly104del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1	P49715-1
CEBPA-DT	ENST00000718467.1 link	n.46+313_46+321delGCCGCCGCC		intron_variant	Intron 1 of 1
ENSG00000267727	ENST00000587312.1 link	n.162_170delCGCCGCCGC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000699

AC:

AN:

142988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000170

AC:

AN:

1179138

Hom.:

AF XY:

0.00000175

AC XY:

AN XY:

572098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24108

American (AMR)

AF:

0.00

AC:

AN:

15604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18770

East Asian (EAS)

AF:

0.00

AC:

AN:

26088

South Asian (SAS)

AF:

0.00

AC:

AN:

42038

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3342

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

963130

Other (OTH)

AF:

0.00

AC:

AN:

46628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000699

AC:

AN:

142988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39540

American (AMR)

AF:

0.00

AC:

AN:

14406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4048

South Asian (SAS)

AF:

0.00

AC:

AN:

3862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65626

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Mar 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.305_313delGCGGCGGCG variant (also known as p.G102_G104del) is located in coding exon 1 of the CEBPA gene. This variant results from an in-frame GCGGCGGCG deletion at nucleotide positions 305 to 313. This results in the in-frame deletion of amino acids at codons 102 to 104. This amino acid region is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear. -

Acute myeloid leukemia

Uncertain:1

Sep 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.305_313del, results in the deletion of 3 amino acid(s) of the CEBPA protein (p.Gly102_Gly104del), 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: 565756). 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

PhyloP100

3.8

Mutation Taster

=190/10

polymorphism

(source)

Splicing

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

Publications

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rs780345232

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over