rs2180197

Positions:

• chr14-24308385-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174913.3(NOP9):​c.*3290C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 194,966 control chromosomes in the GnomAD database, including 86,329 homozygotes. 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: 𝑓 0.94 (66739 hom., cov: 29)
  • Exomes 𝑓: 0.96 (19590 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*3290C>G		3_prime_UTR_variant	10/10	ENST00000267425.8	NP_777573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.*3290C>G		3_prime_UTR_variant	10/10	1	NM_174913.3	ENSP00000267425.3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142251 AN: 151930 Hom.: 66708 Cov.: 29

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.942

GnomAD4 exome AF: 0.955 AC: 40987 AN: 42918 Hom.: 19590 Cov.: 0 AF XY: 0.955 AC XY: 21787 AN XY: 22820

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.941

Gnomad4 ASJ exome AF: 0.965

Gnomad4 EAS exome AF: 0.864

Gnomad4 SAS exome AF: 0.958

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.969

Gnomad4 OTH exome AF: 0.951

GnomAD4 genome AF: 0.936 AC: 142337 AN: 152048 Hom.: 66739 Cov.: 29 AF XY: 0.935 AC XY: 69540 AN XY: 74336

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.943

Alfa AF: 0.947 Hom.: 8478

Bravo AF: 0.930

Asia WGS AF: 0.901 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.67
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

Publications

LitVar

Other links and lift over

dbSNP: rs2180197; hg19: chr14-24777591;