8-47737471-T-A

Variant names:

• chr8-47737471-T-A
• rs11539254
• NM_005195.4:c.650A>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.650A>T​(p.Gln217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. Q217R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEBPD NM_005195.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• 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=0.09054974).

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.650A>T	p.Gln217Leu	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.650A>T	p.Gln217Leu	missense	Exon 1 of 1	ENSP00000386165.3	P49716

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.73	N
PhyloP100		0.84
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.042
Sift	Benign	0.77	T
Sift4G	Benign	0.73	T
Polyphen		0.27	B
Vest4		0.21
MutPred		0.32		Loss of methylation at K222 (P = 0.0416)
MVP		0.40
ClinPred		0.35	T
GERP RS		2.8
Varity_R		0.18
gMVP		0.62
Mutation Taster		=84/16	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: rs11539254; hg19: chr8-48650033;