rs2144492

Positions:

• chr14-24308205-A-C
• chr14-24308205-A-T

Variant summary

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

The NM_174913.3(NOP9):​c.*3110A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 311,668 control chromosomes in the GnomAD database, including 139,598 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 (66800 hom., cov: 32)
  • Exomes 𝑓: 0.96 (72798 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*3110A>C		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.*3110A>C		3_prime_UTR_variant	10/10	1	NM_174913.3	ENSP00000267425.3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142411 AN: 152146 Hom.: 66769 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.941

GnomAD4 exome AF: 0.955 AC: 152243 AN: 159404 Hom.: 72798 Cov.: 0 AF XY: 0.955 AC XY: 82381 AN XY: 86276

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.960

Gnomad4 EAS exome AF: 0.858

Gnomad4 SAS exome AF: 0.957

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.966

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.936 AC: 142497 AN: 152264 Hom.: 66800 Cov.: 32 AF XY: 0.935 AC XY: 69632 AN XY: 74454

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.942

Alfa AF: 0.953 Hom.: 29748

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	-0.82
CADD	Benign	3.8
DANN	Benign	0.66

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: rs2144492; hg19: chr14-24777411;