NM_005194.4:c.146C>A

Variant names:

• chr20-50191179-C-A
• rs761135515
• NM_005194.4:c.146C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005194.4(CEBPB):​c.146C>A​(p.Pro49His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 151,104 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. P49L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEBPB NM_005194.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916
• Publications: 0 publications found

Genes affected

CEBPB (HGNC:1834): (CCAAT enhancer binding protein beta) This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain. The encoded protein functions as a homodimer but can also form heterodimers with CCAAT/enhancer-binding proteins alpha, delta, and gamma. Activity of this protein is important in the regulation of genes involved in immune and inflammatory responses, among other processes. The use of alternative in-frame AUG start codons results in multiple protein isoforms, each with distinct biological functions. [provided by RefSeq, Oct 2013]

CEBPB-AS1 (HGNC:51226): (CEBPB antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2750181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005194.4. 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
	CEBPB	NM_005194.4	MANE Select	c.146C>A	p.Pro49His	missense	Exon 1 of 1	NP_005185.2
	CEBPB	NM_001285878.1		c.77C>A	p.Pro26His	missense	Exon 1 of 1	NP_001272807.1	P17676-2
	CEBPB	NM_001285879.1		c.-449C>A		5_prime_UTR	Exon 1 of 1	NP_001272808.1	P17676-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPB	ENST00000303004.5	TSL:6 MANE Select	c.146C>A	p.Pro49His	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
	CEBPB	ENST00000718336.1		c.146C>A	p.Pro49His	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
	CEBPB-AS1	ENST00000613921.1	TSL:3	n.231+89G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 151104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1292426 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 638170

African (AFR) AF: 0.00 AC: 0 AN: 26304

American (AMR) AF: 0.00 AC: 0 AN: 25334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21884

East Asian (EAS) AF: 0.00 AC: 0 AN: 26698

South Asian (SAS) AF: 0.00 AC: 0 AN: 70762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3904

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028560

Other (OTH) AF: 0.00 AC: 0 AN: 52414

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 151104 Hom.: 0 Cov.: 33 AF XY: 0.0000271 AC XY: 2 AN XY: 73750

African (AFR) AF: 0.0000726 AC: 3 AN: 41322

American (AMR) AF: 0.00 AC: 0 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67608

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		0.92
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.22
MutPred		0.25		Loss of glycosylation at P49 (P = 0.0129)
MVP		0.71
MPC		2.6
ClinPred		0.48	T
GERP RS		1.9
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.17
gMVP		0.29
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: rs761135515; hg19: chr20-48807716;