Genetic Variant CEBPD:p.Pro116Ala (chr8-47737775-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005195.4(CEBPD):c.346C>G(p.Pro116Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,279,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CEBPD
NM_005195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

CEBPD (HGNC:1835): (CCAAT enhancer binding protein delta) The protein encoded by this intronless 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-alpha. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses, and may be involved in the regulation of genes associated with activation and/or differentiation of macrophages. The cytogenetic location of this locus has been reported as both 8p11 and 8q11. [provided by RefSeq, Sep 2010]

CEBPD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09048593).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPD	NM_005195.4 link	c.346C>G	p.Pro116Ala	missense_variant	Exon 1 of 1	ENST00000408965.4	NP_005186.2	P49716

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPD	ENST00000408965.4 link	c.346C>G	p.Pro116Ala	missense_variant	Exon 1 of 1	6	NM_005195.4	ENSP00000386165.3		P49716

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000115

AC:

AN:

1128470

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

545566

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000115

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000948

Gnomad4 OTH exome

AF:

0.0000224

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73734

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.346C>G (p.P116A) alteration is located in exon 1 (coding exon 1) of the CEBPD gene. This alteration results from a C to G substitution at nucleotide position 346, causing the proline (P) at amino acid position 116 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.6

DANN

Benign

0.66

DEOGEN2

Benign

0.23

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.6

REVEL

Benign

0.024

Sift

Benign

0.12

Sift4G

Benign

0.15

Polyphen

0.083

Vest4

0.079

MutPred

0.32

Loss of glycosylation at P116 (P = 0.0342);

MVP

0.24

ClinPred

0.067

GERP RS

1.8

Varity_R

0.038

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over