rs55722931

Variant names:

• chr14-23117586-G-A
• rs55722931
• NM_001805.4:c.747C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23117586-G-A
• chr14-23117586-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001805.4(CEBPE):​c.747C>T​(p.Arg249Arg) 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
• Publications: 2 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 -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 VariationId is 461468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001805.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPE	NM_001805.4	MANE Select	c.747C>T	p.Arg249Arg	synonymous	Exon 2 of 2	NP_001796.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPE	ENST00000206513.6	TSL:1 MANE Select	c.747C>T	p.Arg249Arg	synonymous	Exon 2 of 2	ENSP00000206513.5	Q15744
	CEBPE	ENST00000696121.1		n.716C>T		non_coding_transcript_exon	Exon 3 of 3
	CEBPE	ENST00000696122.1		n.493C>T		non_coding_transcript_exon	Exon 3 of 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

GnomAD2 exomes AF: 0.0152 AC: 3825 AN: 251238 AF XY: 0.0158

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 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

African (AFR) AF: 0.00227 AC: 76 AN: 33480

American (AMR) AF: 0.00617 AC: 276 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0515 AC: 1345 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00943 AC: 813 AN: 86256

European-Finnish (FIN) AF: 0.0258 AC: 1374 AN: 53300

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5766

European-Non Finnish (NFE) AF: 0.0179 AC: 19913 AN: 1112006

Other (OTH) AF: 0.0177 AC: 1071 AN: 60396

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

African (AFR) AF: 0.00267 AC: 111 AN: 41572

American (AMR) AF: 0.00731 AC: 112 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 188 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4830

European-Finnish (FIN) AF: 0.0306 AC: 325 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1229 AN: 68026

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.0170 Hom.: 41

Bravo AF: 0.0116

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0186

EpiControl AF: 0.0196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CEBPE-related disorder (1)
-	-	1	not provided (1)
-	-	1	Specific granule deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.82
Mutation Taster		=100/0	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: rs55722931; hg19: chr14-23586795;