Variant 8-47737616-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005195.4(CEBPD):c.505A>G(p.Arg169Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000467 in 1,311,028 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

CEBPD
NM_005195.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.284

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020512044).

BP6

Variant 8-47737616-T-C is Benign according to our data. Variant chr8-47737616-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2367192.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 99 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPD	NM_005195.4 linkuse as main transcript	c.505A>G	p.Arg169Gly	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.505A>G	p.Arg169Gly	missense_variant	1/1	6	NM_005195.4	ENSP00000386165.3		P49716

Frequencies

GnomAD3 genomes

AF:

0.000654

AC:

AN:

151322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00356

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000501

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00181

AC:

AN:

7726

Hom.:

AF XY:

0.00135

AC XY:

AN XY:

4448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000442

AC:

513

AN:

1159600

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

254

AN XY:

557350

show subpopulations

Gnomad4 AFR exome

AF:

0.000173

Gnomad4 AMR exome

AF:

0.00252

Gnomad4 ASJ exome

AF:

0.000130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000318

GnomAD4 genome

AF:

0.000654

AC:

AN:

151428

Hom.:

Cov.:

AF XY:

0.000770

AC XY:

AN XY:

74018

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00355

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000501

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000832

Hom.:

Bravo

AF:

0.000691

ExAC

AF:

0.0000312

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.22

M_CAP

Benign

0.010

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.78

REVEL

Benign

0.020

Sift

Benign

0.42

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.028

MVP

0.068

ClinPred

0.012

GERP RS

0.84

Varity_R

0.074

gMVP

0.41

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