NM_005195.4:c.512C>T

Variant names:

• chr8-47737609-G-A
• rs769172758
• NM_005195.4:c.512C>T

Variant summary

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

The NM_005195.4(CEBPD):​c.512C>T​(p.Thr171Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,289,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T171N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: CEBPD NM_005195.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 0 publications found

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]

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=0.068974644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005195.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPD	NM_005195.4	MANE Select	c.512C>T	p.Thr171Ile	missense	Exon 1 of 1	NP_005186.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPD	ENST00000408965.4	TSL:6 MANE Select	c.512C>T	p.Thr171Ile	missense	Exon 1 of 1	ENSP00000386165.3	P49716

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000310 AC: 4 AN: 1289442 Hom.: 0 Cov.: 31 AF XY: 0.00000317 AC XY: 2 AN XY: 631024

African (AFR) AF: 0.00 AC: 0 AN: 25476

American (AMR) AF: 0.00 AC: 0 AN: 21478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19220

East Asian (EAS) AF: 0.00 AC: 0 AN: 29330

South Asian (SAS) AF: 0.00 AC: 0 AN: 63238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3688

European-Non Finnish (NFE) AF: 0.00000386 AC: 4 AN: 1035722

Other (OTH) AF: 0.00 AC: 0 AN: 53300

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.75
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.029
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.068
MutPred		0.24		Loss of phosphorylation at T171 (P = 0.0014)
MVP		0.20
ClinPred		0.078	T
GERP RS		-6.6
Varity_R		0.046
gMVP		0.46
Mutation Taster		=96/4	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: rs769172758; hg19: chr8-48650171;