rs1555742243

Variant names:

• chr19-33302159-G-A
• rs1555742243
• NM_004364.5:c.256C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-33302159-G-A
• chr19-33302159-G-C
• chr19-33302159-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001285829.2(CEBPA):​c.-102C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,435,626 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 Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CEBPA NM_001285829.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.03
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34892172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001285829.2. 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.256C>T	p.Arg86Trp	missense	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001285829.2		c.-102C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001272758.1	P49715-3
	CEBPA	NM_001287424.2		c.361C>T	p.Arg121Trp	missense	Exon 1 of 1	NP_001274353.1	P49715-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.256C>T	p.Arg86Trp	missense	Exon 1 of 1	ENSP00000427514.1	P49715-1
	CEBPA-DT	ENST00000718467.1		n.46+360G>A		intron	N/A
	ENSG00000267727	ENST00000587312.1	TSL:3	n.*219G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151380 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.79e-7 AC: 1 AN: 1284246 Hom.: 0 Cov.: 33 AF XY: 0.00000158 AC XY: 1 AN XY: 631960

African (AFR) AF: 0.0000377 AC: 1 AN: 26496

American (AMR) AF: 0.00 AC: 0 AN: 25256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21906

East Asian (EAS) AF: 0.00 AC: 0 AN: 27530

South Asian (SAS) AF: 0.00 AC: 0 AN: 64052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017138

Other (OTH) AF: 0.00 AC: 0 AN: 51862

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151380 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73918

African (AFR) AF: 0.0000726 AC: 3 AN: 41332

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67816

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	0.0085
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.093
Sift	Uncertain	0.017	D
Sift4G	Benign	0.085	T
Polyphen		0.99	D
Vest4		0.13
MutPred		0.32		Loss of disorder (P = 0.0195)
MVP		0.48
ClinPred		0.73	D
GERP RS		3.0
PromoterAI		-0.063	Neutral
Varity_R		0.14
gMVP		0.29
Mutation Taster		=80/20	polymorphism

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: rs1555742243; hg19: chr19-33793065;