Variant 8-47737414-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005195.4(CEBPD):c.707G>A(p.Arg236His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,452,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CEBPD
NM_005195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.476

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38534102).

BS2

High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPD	NM_005195.4 linkuse as main transcript	c.707G>A	p.Arg236His	missense_variant	1/1	ENST00000408965.4	NP_005186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPD	ENST00000408965.4 linkuse as main transcript	c.707G>A	p.Arg236His	missense_variant	1/1		NM_005195.4	ENSP00000386165	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000433

AC:

AN:

231138

Hom.:

AF XY:

0.0000394

AC XY:

AN XY:

126994

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

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:

0.0000682

Gnomad OTH exome

AF:

0.000355

GnomAD4 exome

AF:

0.0000461

AC:

AN:

1452694

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

722416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000453

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:

0.0000559

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

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

Jun 17, 2022

The c.707G>A (p.R236H) alteration is located in exon 1 (coding exon 1) of the CEBPD gene. This alteration results from a G to A substitution at nucleotide position 707, causing the arginine (R) at amino acid position 236 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.99

Vest4

0.25

MVP

0.60

ClinPred

0.74

GERP RS

2.7

Varity_R

0.28

gMVP

0.59

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