chr14-24307138-T-A

Variant names:

• chr14-24307138-T-A
• rs1053648
• NM_174913.3:c.*2043T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174913.3(NOP9):​c.*2043T>A variant causes a 3 prime UTR 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 5 publications found

Genes affected

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]

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]

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174913.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	NM_174913.3	MANE Select	c.*2043T>A		3_prime_UTR	Exon 10 of 10	NP_777573.1
	CIDEB	NM_001393339.1	MANE Select	c.186+233A>T		intron	N/A	NP_001380268.1
	NOP9	NM_001286367.2		c.*2180T>A		3_prime_UTR	Exon 10 of 10	NP_001273296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.*2043T>A		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3
	CIDEB	ENST00000554411.6	TSL:1 MANE Select	c.186+233A>T		intron	N/A	ENSP00000451089.1
	CIDEB	ENST00000258807.5	TSL:1	c.186+233A>T		intron	N/A	ENSP00000258807.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 258050 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 132676

African (AFR) AF: 0.00 AC: 0 AN: 7498

American (AMR) AF: 0.00 AC: 0 AN: 9592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9116

East Asian (EAS) AF: 0.00 AC: 0 AN: 22004

South Asian (SAS) AF: 0.00 AC: 0 AN: 10790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 161672

Other (OTH) AF: 0.00 AC: 0 AN: 16362

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 78263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.59
PhyloP100		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1053648; hg19: chr14-24776344;