rs1060504475

Variant names:

• chr19-33302019-G-A
• rs1060504475
• NM_004364.5:c.396C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-33302019-G-A
• chr19-33302019-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004364.5(CEBPA):​c.396C>T​(p.Gly132Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,180,774 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 3.12
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-33302019-G-A is Benign according to our data. Variant chr19-33302019-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 415194.
• BP7: Synonymous conserved (PhyloP=3.12 with no splicing effect.
• BS2: High AC in GnomAd4 at 12 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	NM_004364.5	MANE Select	c.396C>T	p.Gly132Gly	synonymous	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.501C>T	p.Gly167Gly	synonymous	Exon 1 of 1	NP_001274353.1
	CEBPA	NM_001287435.2		c.354C>T	p.Gly118Gly	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.396C>T	p.Gly132Gly	synonymous	Exon 1 of 1	ENSP00000427514.1
	CEBPA-DT	ENST00000718467.1		n.46+220G>A		intron	N/A
	ENSG00000267727	ENST00000587312.1	TSL:3	n.*79G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000807 AC: 12 AN: 148640 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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: 0.000120

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2718 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ 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: 0.000225 AC: 232 AN: 1032134 Hom.: 0 Cov.: 33 AF XY: 0.000219 AC XY: 107 AN XY: 487844

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

American (AMR) AF: 0.00 AC: 0 AN: 6550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11616

East Asian (EAS) AF: 0.00 AC: 0 AN: 21346

South Asian (SAS) AF: 0.00 AC: 0 AN: 20202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2612

European-Non Finnish (NFE) AF: 0.000260 AC: 231 AN: 886940

Other (OTH) AF: 0.0000254 AC: 1 AN: 39430

GnomAD4 genome AF: 0.0000807 AC: 12 AN: 148640 Hom.: 0 Cov.: 32 AF XY: 0.000110 AC XY: 8 AN XY: 72458

African (AFR) AF: 0.0000488 AC: 2 AN: 41022

American (AMR) AF: 0.000133 AC: 2 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9304

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

European-Non Finnish (NFE) AF: 0.000120 AC: 8 AN: 66764

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Acute myeloid leukemia (1)
-	1	-	Hereditary cancer-predisposing syndrome (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		3.1

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: rs1060504475; hg19: chr19-33792925;