19-33302235-C-T

Variant names:

• chr19-33302235-C-T
• rs1243562179
• NM_004364.5:c.180G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004364.5(CEBPA):​c.180G>A​(p.Thr60Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000745 in 1,341,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T60T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• 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)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	NM_004364.5	MANE Select	c.180G>A	p.Thr60Thr	synonymous	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.285G>A	p.Thr95Thr	synonymous	Exon 1 of 1	NP_001274353.1
	CEBPA	NM_001287435.2		c.138G>A	p.Thr46Thr	synonymous	Exon 1 of 1	NP_001274364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.180G>A	p.Thr60Thr	synonymous	Exon 1 of 1	ENSP00000427514.1
	CEBPA-DT	ENST00000718467.1		n.46+436C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1341862 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 661774

African (AFR) AF: 0.00 AC: 0 AN: 27176

American (AMR) AF: 0.00 AC: 0 AN: 29648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23374

East Asian (EAS) AF: 0.00 AC: 0 AN: 29642

South Asian (SAS) AF: 0.00 AC: 0 AN: 73662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050624

Other (OTH) AF: 0.00 AC: 0 AN: 55146

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		1.5
PromoterAI		-0.036	Neutral

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: rs1243562179; hg19: chr19-33793141;