chr19-33302101-T-TCGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_004364.5(CEBPA):c.311_313dupGCG(p.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 0.0000976 in 1,322,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D105D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:3

Conservation

PhyloP100: 2.85

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004364.5

BP6

Variant 19-33302101-T-TCGC is Benign according to our data. Variant chr19-33302101-T-TCGC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 408748.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CEBPA	NM_004364.5 link	c.311_313dupGCG	p.Gly104dup	conservative_inframe_insertion	Exon 1 of 1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001287424.2 link	c.416_418dupGCG	p.Gly139dup	conservative_inframe_insertion	Exon 1 of 1		NP_001274353.1
CEBPA	NM_001287435.2 link	c.269_271dupGCG	p.Gly90dup	conservative_inframe_insertion	Exon 1 of 1		NP_001274364.1
CEBPA	NM_001285829.2 link	c.-47_-45dupGCG		5_prime_UTR_variant	Exon 1 of 1		NP_001272758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CEBPA	ENST00000498907.3 link	c.311_313dupGCG	p.Gly104dup	conservative_inframe_insertion	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1
CEBPA-DT	ENST00000718467.1 link	n.46+319_46+321dupGCC		intron_variant	Intron 1 of 1
ENSG00000267727	ENST00000587312.1 link	n.161_162insCGC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000769

AC:

AN:

142988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00236

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000400

AC:

AN:

54968

AF XY:

0.000433

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000169

Gnomad ASJ exome

AF:

0.00316

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.000725

GnomAD4 exome

AF:

0.000100

AC:

118

AN:

1179146

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

572104

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

24108

American (AMR)

AF:

0.000192

AC:

AN:

15606

Ashkenazi Jewish (ASJ)

AF:

0.00250

AC:

AN:

18770

East Asian (EAS)

AF:

0.000153

AC:

AN:

26088

South Asian (SAS)

AF:

0.000262

AC:

AN:

42038

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3342

European-Non Finnish (NFE)

AF:

0.0000436

AC:

AN:

963136

Other (OTH)

AF:

0.000150

AC:

AN:

46630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000769

AC:

AN:

142988

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

69714

show subpopulations

African (AFR)

AF:

0.0000253

AC:

AN:

39540

American (AMR)

AF:

0.00

AC:

AN:

14406

Ashkenazi Jewish (ASJ)

AF:

0.00236

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:

0.0000305

AC:

AN:

65626

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000106

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Acute myeloid leukemia

Pathogenic:1Uncertain:1Benign:1

Dec 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genomic Diagnostics Laboratory, National Institute of Medical Genomics

Significance:Likely pathogenic

Review Status:flagged submission

Collection Method:clinical testing

The variant was detected in bone marrow from patients, but it was not confirmed in the matched -

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Inborn genetic diseases

Benign:1

Mar 20, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary cancer-predisposing syndrome

Benign:1

Dec 03, 2020

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=79/21

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over