rs1400432198

Variant names:

• chr2-37202812-C-A
• rs1400432198
• NM_005760.3:c.2997G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-37202812-C-A
• chr2-37202812-C-T

Variant summary

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

The NM_005760.3(CEBPZ):​c.2997G>T​(p.Met999Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,776 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M999L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEBPZ NM_005760.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

Genes affected

CEBPZ (HGNC:24218): (CCAAT enhancer binding protein zeta) This gene belongs to the CBF/Mak21 family. The encoded protein plays a role in cellular response to environmental stimuli through a transcriptional process that involves heat shock factors, conserved DNA elements (heat shock elements or HSEs) and CCAAT boxes. The protein acts as a DNA-binding transcriptional activator and regulates the heat-shock protein 70 (HSP70) promoter in a CCAAT-dependent manner. The protein is also involved in cell growth and differentiation, particularly, hematopoietic differentiation. [provided by RefSeq, Nov 2020]

CEBPZOS (HGNC:49288): (CEBPZ opposite strand) Predicted to be located in mitochondrial membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1533618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005760.3. 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
	CEBPZ	NM_005760.3	MANE Select	c.2997G>T	p.Met999Ile	missense	Exon 15 of 16	NP_005751.2
	CEBPZOS	NM_001322374.2	MANE Select	c.*952C>A		3_prime_UTR	Exon 5 of 5	NP_001309303.1	A8MTT3
	CEBPZOS	NM_001322373.2		c.*952C>A		3_prime_UTR	Exon 6 of 6	NP_001309302.1	A8MTT3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPZ	ENST00000234170.10	TSL:1 MANE Select	c.2997G>T	p.Met999Ile	missense	Exon 15 of 16	ENSP00000234170.5	Q03701
	CEBPZOS	ENST00000402297.6	TSL:2 MANE Select	c.*952C>A		3_prime_UTR	Exon 5 of 5	ENSP00000384331.1	A8MTT3
	CEBPZ	ENST00000898579.1		c.3015G>T	p.Met1005Ile	missense	Exon 15 of 16	ENSP00000568638.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440776 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716210

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32594

American (AMR) AF: 0.00 AC: 0 AN: 42124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 38896

South Asian (SAS) AF: 0.00 AC: 0 AN: 82146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5246

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101902

Other (OTH) AF: 0.00 AC: 0 AN: 59380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.063
Sift	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.0040	B
Vest4		0.29
MutPred		0.31		Loss of disorder (P = 0.0402)
MVP		0.52
MPC		0.017
ClinPred		0.63	D
GERP RS		4.0
Varity_R		0.11
gMVP		0.25
Mutation Taster		=91/9	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: rs1400432198; hg19: chr2-37429955;