chr20-50191785-G-C

Variant names:

• chr20-50191785-G-C
• rs1361582241
• NM_005194.4:c.752G>C

Variant summary

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

The NM_005194.4(CEBPB):​c.752G>C​(p.Gly251Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,547,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G251E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CEBPB NM_005194.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.772
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15595329).

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.752G>C	p.Gly251Ala	missense	Exon 1 of 1	NP_005185.2
	CEBPB	NM_001285878.1		c.683G>C	p.Gly228Ala	missense	Exon 1 of 1	NP_001272807.1	P17676-2
	CEBPB	NM_001285879.1		c.158G>C	p.Gly53Ala	missense	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.752G>C	p.Gly251Ala	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
	CEBPB	ENST00000718336.1		c.752G>C	p.Gly251Ala	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
	CEBPB-AS1	ENST00000751366.1		n.118+137C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152030 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000667 AC: 1 AN: 150020 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1395802 Hom.: 0 Cov.: 33 AF XY: 0.00000435 AC XY: 3 AN XY: 689316

African (AFR) AF: 0.00 AC: 0 AN: 30702

American (AMR) AF: 0.00 AC: 0 AN: 35472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 35162

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5362

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079560

Other (OTH) AF: 0.00 AC: 0 AN: 57888

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152030 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.77
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.058
Sift	Benign	0.16	T
Sift4G	Uncertain	0.026	D
Polyphen		0.056	B
Vest4		0.17
MutPred		0.20		Gain of loop (P = 0.0121)
MVP		0.17
MPC		1.5
ClinPred		0.069	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.55
Mutation Taster		=67/33	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: rs1361582241; hg19: chr20-48808322;