11-85664374-T-C

Position:

• chr11-85664374-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039618.4(CREBZF):​c.502A>G​(p.Asn168Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CREBZF NM_001039618.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

CREBZF (HGNC:24905): (CREB/ATF bZIP transcription factor) Enables identical protein binding activity. Involved in negative regulation of gene expression, epigenetic; regulation of transcription, DNA-templated; and response to virus. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CREBZF (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18312383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREBZF	NM_001039618.4	c.502A>G	p.Asn168Asp	missense_variant	1/1	ENST00000527447.2	NP_001034707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREBZF	ENST00000527447.2	c.502A>G	p.Asn168Asp	missense_variant	1/1	6	NM_001039618.4	ENSP00000433459.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461528 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.502A>G (p.N168D) alteration is located in exon 1 (coding exon 1) of the CREBZF gene. This alteration results from a A to G substitution at nucleotide position 502, causing the asparagine (N) at amino acid position 168 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.11	N
REVEL	Benign	0.11
Sift	Benign	0.15	T
Sift4G	Benign	0.075	T
Polyphen		0.99	D
Vest4		0.15
MutPred		0.099		Loss of MoRF binding (P = 0.0738);
MVP		0.16
MPC		0.77
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-85375418;