rs55722931

Positions:

• chr14-23117586-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001805.4(CEBPE):​c.747C>T​(p.Arg249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,614,098 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (24 hom., cov: 32)
  • Exomes 𝑓: 0.017 (275 hom.)
• Consequence: CEBPE NM_001805.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.820

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-23117586-G-A is Benign according to our data. Variant chr14-23117586-G-A is described in ClinVar as [Benign]. Clinvar id is 461468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23117586-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2049/152334) while in subpopulation NFE AF= 0.0181 (1229/68026). AF 95% confidence interval is 0.0172. There are 24 homozygotes in gnomad4. There are 1051 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPE	NM_001805.4	c.747C>T	p.Arg249=	synonymous_variant	2/2	ENST00000206513.6	NP_001796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPE	ENST00000206513.6	c.747C>T	p.Arg249=	synonymous_variant	2/2	1	NM_001805.4	ENSP00000206513	P1
CEBPE	ENST00000696121.1	n.716C>T		non_coding_transcript_exon_variant	3/3
CEBPE	ENST00000696122.1	n.493C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2049 AN: 152216 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00732

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.0152 AC: 3825 AN: 251238 Hom.: 50 AF XY: 0.0158 AC XY: 2152 AN XY: 135838

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.0491

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00928

Gnomad FIN exome AF: 0.0273

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0171 AC: 24946 AN: 1461764 Hom.: 275 Cov.: 32 AF XY: 0.0171 AC XY: 12405 AN XY: 727220

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00617

Gnomad4 ASJ exome AF: 0.0515

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00943

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0177

GnomAD4 genome AF: 0.0135 AC: 2049 AN: 152334 Hom.: 24 Cov.: 32 AF XY: 0.0141 AC XY: 1051 AN XY: 74496

Gnomad4 AFR AF: 0.00267

Gnomad4 AMR AF: 0.00731

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0172 Hom.: 13

Bravo AF: 0.0116

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0186

EpiControl AF: 0.0196

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Specific granule deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

CEBPE-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.9
DANN	Benign	0.70

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: rs55722931; hg19: chr14-23586795;