rs1345901618

Variant names:

• chr19-33301782-C-A
• rs1345901618
• NM_004364.5:c.633G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-33301782-C-A
• chr19-33301782-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_004364.5(CEBPA):​c.633G>T​(p.Ala211Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,215,630 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. A211A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.197
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 19-33301782-C-A is Benign according to our data. Variant chr19-33301782-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 456695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.197 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5	c.633G>T	p.Ala211Ala	synonymous_variant	Exon 1 of 1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001287424.2	c.738G>T	p.Ala246Ala	synonymous_variant	Exon 1 of 1		NP_001274353.1
CEBPA	NM_001287435.2	c.591G>T	p.Ala197Ala	synonymous_variant	Exon 1 of 1		NP_001274364.1
CEBPA	NM_001285829.2	c.276G>T	p.Ala92Ala	synonymous_variant	Exon 1 of 1		NP_001272758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3	c.633G>T	p.Ala211Ala	synonymous_variant	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1
CEBPA-DT	ENST00000718467.1	n.29C>A		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000267727	ENST00000587312.1	n.357-33C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.00000674 AC: 1 AN: 148450 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

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: 0.00000375 AC: 4 AN: 1067180 Hom.: 0 Cov.: 22 AF XY: 0.00000195 AC XY: 1 AN XY: 512736

African (AFR) AF: 0.00 AC: 0 AN: 21182

American (AMR) AF: 0.00 AC: 0 AN: 7106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12394

East Asian (EAS) AF: 0.00 AC: 0 AN: 22854

South Asian (SAS) AF: 0.00 AC: 0 AN: 27576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2744

European-Non Finnish (NFE) AF: 0.00000329 AC: 3 AN: 910852

Other (OTH) AF: 0.0000242 AC: 1 AN: 41368

GnomAD4 genome AF: 0.00000674 AC: 1 AN: 148450 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72362

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40994

American (AMR) AF: 0.0000669 AC: 1 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9186

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66732

Other (OTH) AF: 0.00 AC: 0 AN: 2034

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acute myeloid leukemia Benign:1

Feb 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.20

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: rs1345901618; hg19: chr19-33792688;