chr14-23118605-C-A

Variant names:

• chr14-23118605-C-A
• rs762842144
• NM_001805.4:c.487G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001805.4(CEBPE):​c.487G>T​(p.Gly163Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G163S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEBPE NM_001805.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20277113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPE	NM_001805.4	c.487G>T	p.Gly163Cys	missense_variant	Exon 1 of 2	ENST00000206513.6	NP_001796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPE	ENST00000206513.6	c.487G>T	p.Gly163Cys	missense_variant	Exon 1 of 2	1	NM_001805.4	ENSP00000206513.5
CEBPE	ENST00000696121.1	n.456G>T		non_coding_transcript_exon_variant	Exon 2 of 3
CEBPE	ENST00000696122.1	n.233G>T		non_coding_transcript_exon_variant	Exon 2 of 3
ENSG00000295888	ENST00000733532.1	n.234+3187C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.60
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.035
Sift	Benign	0.079	T
Sift4G	Uncertain	0.023	D
Polyphen		0.62	P
Vest4		0.22
MutPred		0.42		Gain of catalytic residue at P162 (P = 0);
MVP		0.66
MPC		0.21
ClinPred		0.54	D
GERP RS		3.1
Varity_R		0.16
gMVP		0.43
Mutation Taster		=94/6	polymorphism

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: rs762842144; hg19: chr14-23587814;