19-33302028-G-C

Variant names:

• chr19-33302028-G-C
• rs1060504477
• NM_004364.5:c.387C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004364.5(CEBPA):​c.387C>G​(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,182,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.642
• 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]

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

ENSG00000267727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-33302028-G-C is Benign according to our data. Variant chr19-33302028-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 415198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.642 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 25 AD gene.

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.387C>G	p.Pro129Pro	synonymous	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.492C>G	p.Pro164Pro	synonymous	Exon 1 of 1	NP_001274353.1	P49715-4
	CEBPA	NM_001287435.2		c.345C>G	p.Pro115Pro	synonymous	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.387C>G	p.Pro129Pro	synonymous	Exon 1 of 1	ENSP00000427514.1	P49715-1
	CEBPA-DT	ENST00000718467.1		n.46+229G>C		intron	N/A
	ENSG00000267727	ENST00000587312.1	TSL:3	n.*88G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000202 AC: 3 AN: 148758 Hom.: 0 Cov.: 32

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: 0.0000449

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 3638 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000242 AC: 25 AN: 1033418 Hom.: 0 Cov.: 33 AF XY: 0.0000266 AC XY: 13 AN XY: 488366

African (AFR) AF: 0.00 AC: 0 AN: 20680

American (AMR) AF: 0.00 AC: 0 AN: 6566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11646

East Asian (EAS) AF: 0.00 AC: 0 AN: 21330

South Asian (SAS) AF: 0.0000500 AC: 1 AN: 20018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2618

European-Non Finnish (NFE) AF: 0.0000271 AC: 24 AN: 887200

Other (OTH) AF: 0.00 AC: 0 AN: 39518

GnomAD4 genome AF: 0.0000202 AC: 3 AN: 148758 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 2 AN XY: 72500

African (AFR) AF: 0.00 AC: 0 AN: 41022

American (AMR) AF: 0.00 AC: 0 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66860

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Acute myeloid leukemia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		-0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1060504477; hg19: chr19-33792934;