chr20-50191148-G-C

Variant names:

• chr20-50191148-G-C
• rs1241425543
• NM_005194.4:c.115G>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.115G>C​(p.Ala39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 1,514,980 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A39T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CEBPB NM_005194.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19148138).

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.115G>C	p.Ala39Pro	missense	Exon 1 of 1	NP_005185.2
	CEBPB	NM_001285878.1		c.46G>C	p.Ala16Pro	missense	Exon 1 of 1	NP_001272807.1	P17676-2
	CEBPB	NM_001285879.1		c.-480G>C		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.115G>C	p.Ala39Pro	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
	CEBPB	ENST00000718336.1		c.115G>C	p.Ala39Pro	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
	CEBPB-AS1	ENST00000613921.1	TSL:3	n.231+120C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151640 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: 0.00000672 AC: 1 AN: 148904 AF XY: 0.00

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: 0.0000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1363340 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 677562

African (AFR) AF: 0.00 AC: 0 AN: 28116

American (AMR) AF: 0.00 AC: 0 AN: 33806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23388

East Asian (EAS) AF: 0.00 AC: 0 AN: 30632

South Asian (SAS) AF: 0.00 AC: 0 AN: 77492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4360

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1067854

Other (OTH) AF: 0.00 AC: 0 AN: 55562

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151640 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74060

African (AFR) AF: 0.00 AC: 0 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67834

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.050
Sift	Benign	0.24	T
Sift4G	Benign	0.087	T
Polyphen		0.70	P
Vest4		0.35
MutPred		0.37		Loss of helix (P = 0.0138)
MVP		0.41
MPC		1.9
ClinPred		0.15	T
GERP RS		1.9
PromoterAI		-0.074	Neutral
Varity_R		0.19
gMVP		0.32
Mutation Taster		=78/22	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: rs1241425543; hg19: chr20-48807685;