rs12434881

Positions:

• chr14-23119433-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696121.1(CEBPE):​n.261+563C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 305,462 control chromosomes in the GnomAD database, including 24,363 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11057 hom., cov: 31)
  • Exomes 𝑓: 0.40 (13306 hom.)
• Consequence: CEBPE ENST00000696121.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

Genes affected

CEBPE (HGNC:1836): (CCAAT enhancer binding protein epsilon) The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-delta. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with Specific Granule Deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPE	ENST00000696121.1	n.261+563C>T		intron_variant, non_coding_transcript_variant
CEBPE	ENST00000696122.1	n.42+224C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55433 AN: 151894 Hom.: 11052 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.404 AC: 61958 AN: 153452 Hom.: 13306 Cov.: 0 AF XY: 0.400 AC XY: 32039 AN XY: 80094

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.365 AC: 55466 AN: 152010 Hom.: 11057 Cov.: 31 AF XY: 0.362 AC XY: 26872 AN XY: 74302

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.350

Alfa AF: 0.424 Hom.: 13948

Bravo AF: 0.352

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs12434881; hg19: chr14-23588642;