rs12434881

Variant names:

• chr14-23119433-G-A
• rs12434881
• ENST00000696121.1:n.261+563C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696121.1(CEBPE):​n.261+563C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 10 publications found

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]

CEBPE Gene-Disease associations (from GenCC):

• specific granule deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• specific granule deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000295888 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CEBPE	NM_001805.4	c.-342C>T		upstream_gene_variant		ENST00000206513.6	NP_001796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPE	ENST00000696121.1	n.261+563C>T		intron_variant	Intron 1 of 2
CEBPE	ENST00000696122.1	n.42+224C>T		intron_variant	Intron 1 of 2
ENSG00000295888	ENST00000733532.1	n.234+4015G>A		intron_variant	Intron 1 of 1
CEBPE	ENST00000206513.6	c.-342C>T		upstream_gene_variant		1	NM_001805.4	ENSP00000206513.5

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

African (AFR) AF: 0.195 AC: 1020 AN: 5218

American (AMR) AF: 0.385 AC: 2245 AN: 5828

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1616 AN: 4586

East Asian (EAS) AF: 0.314 AC: 2805 AN: 8930

South Asian (SAS) AF: 0.333 AC: 5818 AN: 17488

European-Finnish (FIN) AF: 0.407 AC: 3320 AN: 8152

Middle Eastern (MID) AF: 0.281 AC: 190 AN: 676

European-Non Finnish (NFE) AF: 0.443 AC: 41424 AN: 93510

Other (OTH) AF: 0.388 AC: 3520 AN: 9064

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

African (AFR) AF: 0.201 AC: 8329 AN: 41466

American (AMR) AF: 0.402 AC: 6142 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1240 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1424 AN: 5148

South Asian (SAS) AF: 0.360 AC: 1734 AN: 4822

European-Finnish (FIN) AF: 0.403 AC: 4261 AN: 10564

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31020 AN: 67936

Other (OTH) AF: 0.350 AC: 740 AN: 2112

Alfa AF: 0.414 Hom.: 17534

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
PhyloP100		1.8
PromoterAI		0.022	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs12434881; hg19: chr14-23588642;