NM_005194.4:c.372C>T

Variant names:

• chr20-50191405-C-T
• rs773801449
• NM_005194.4:c.372C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005194.4(CEBPB):​c.372C>T​(p.Asp124Asp) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEBPB NM_005194.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.988 with no splicing effect.

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.372C>T	p.Asp124Asp	synonymous	Exon 1 of 1	NP_005185.2
	CEBPB	NM_001285879.1		c.-223C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001272808.1	P17676-3
	CEBPB	NM_001285878.1		c.303C>T	p.Asp101Asp	synonymous	Exon 1 of 1	NP_001272807.1	P17676-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPB	ENST00000303004.5	TSL:6 MANE Select	c.372C>T	p.Asp124Asp	synonymous	Exon 1 of 1	ENSP00000305422.3	P17676-1
	CEBPB	ENST00000718336.1		c.372C>T	p.Asp124Asp	synonymous	Exon 1 of 1	ENSP00000520773.1	P17676-1
	CEBPB-AS1	ENST00000613921.1	TSL:3	n.94G>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366584 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 677158

African (AFR) AF: 0.00 AC: 0 AN: 27794

American (AMR) AF: 0.00 AC: 0 AN: 35342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23250

East Asian (EAS) AF: 0.00 AC: 0 AN: 30384

South Asian (SAS) AF: 0.00 AC: 0 AN: 78536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062488

Other (OTH) AF: 0.00 AC: 0 AN: 55416

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.88
PhyloP100		0.99

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: rs773801449; hg19: chr20-48807942; COSMIC: COSV57277039;