Variant chr8-47737601-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005195.4(CEBPD):c.520C>A(p.Pro174Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

CEBPD
NM_005195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14942625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPD	NM_005195.4 linkuse as main transcript	c.520C>A	p.Pro174Thr	missense_variant	1/1	ENST00000408965.4	NP_005186.2	P49716

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPD	ENST00000408965.4 linkuse as main transcript	c.520C>A	p.Pro174Thr	missense_variant	1/1	6	NM_005195.4	ENSP00000386165.3		P49716

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000535

AC:

AN:

56028

Hom.:

AF XY:

0.00

AC XY:

AN XY:

30886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000265

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000229

AC:

AN:

1307268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

640970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151754

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.520C>A (p.P174T) alteration is located in exon 1 (coding exon 1) of the CEBPD gene. This alteration results from a C to A substitution at nucleotide position 520, causing the proline (P) at amino acid position 174 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.9

REVEL

Benign

0.036

Sift

Benign

0.23

Sift4G

Benign

0.085

Polyphen

0.23

Vest4

0.066

MutPred

0.16

Gain of phosphorylation at P174 (P = 0.0163);

MVP

0.30

ClinPred

0.048

GERP RS

0.56

Varity_R

0.12

gMVP

0.40

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