14-24307195-C-G

Variant names:

• chr14-24307195-C-G
• rs1053649
• NM_174913.3:c.*2100C>G

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.*2100C>G 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: 31)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 6 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*2100C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1
CIDEB	NM_001393339.1	c.186+176G>C		intron_variant	Intron 2 of 4	ENST00000554411.6	NP_001380268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.*2100C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3
CIDEB	ENST00000554411.6	c.186+176G>C		intron_variant	Intron 2 of 4	1	NM_001393339.1	ENSP00000451089.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000432 AC: 2 AN: 463476 Hom.: 0 Cov.: 6 AF XY: 0.00000832 AC XY: 2 AN XY: 240322

African (AFR) AF: 0.00 AC: 0 AN: 12258

American (AMR) AF: 0.00 AC: 0 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12586

East Asian (EAS) AF: 0.0000343 AC: 1 AN: 29190

South Asian (SAS) AF: 0.00 AC: 0 AN: 35994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1888

European-Non Finnish (NFE) AF: 0.00000338 AC: 1 AN: 295594

Other (OTH) AF: 0.00 AC: 0 AN: 25124

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.22
PhyloP100		-0.22

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: rs1053649; hg19: chr14-24776401;