14-24306457-C-T

Position:

• chr14-24306457-C-T

Variant summary

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

The NM_001393339.1(CIDEB):​c.253G>A​(p.Asp85Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIDEB NM_001393339.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

Genes affected

CIDEB (HGNC:1977): (cell death inducing DFFA like effector b) Enables identical protein binding activity. Involved in activation of cysteine-type endopeptidase activity; positive regulation of cell death; and positive regulation of release of cytochrome c from mitochondria. Acts upstream of or within apoptotic process. Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LTB4R2 (HGNC:19260): (leukotriene B4 receptor 2) Predicted to enable G protein-coupled peptide receptor activity and leukotriene B4 receptor activity. Predicted to be involved in inflammatory response and neuropeptide signaling pathway. Predicted to act upstream of or within keratinocyte migration and signal transduction. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEB	NM_001393339.1	c.253G>A	p.Asp85Asn	missense_variant	3/5	ENST00000554411.6	NP_001380268.1
NOP9	NM_174913.3	c.*1362C>T		3_prime_UTR_variant	10/10	ENST00000267425.8	NP_777573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIDEB	ENST00000554411.6	c.253G>A	p.Asp85Asn	missense_variant	3/5	1	NM_001393339.1	ENSP00000451089.1
NOP9	ENST00000267425.8	c.*1362C>T		3_prime_UTR_variant	10/10	1	NM_174913.3	ENSP00000267425.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

Nov 14, 2024

The c.253G>A (p.D85N) alteration is located in exon 5 (coding exon 3) of the CIDEB gene. This alteration results from a G to A substitution at nucleotide position 253, causing the aspartic acid (D) at amino acid position 85 to be replaced by an asparagine (N). 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	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;D;D
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.42	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.027	B;B;B
Vest4		0.27
MutPred		0.72		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.62
MPC		0.17
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.44
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2041510457; hg19: chr14-24775663;