Genetic Variant NOP9:c.*2043T>C (chr14-24307138-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_174913.3(NOP9):c.*2043T>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 0.948 in 410,166 control chromosomes in the GnomAD database, including 184,548 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 ( 67733 hom., cov: 32)

Exomes 𝑓: 0.95 ( 116815 hom. )

Consequence

NOP9
NM_174913.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Variant links:

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]

NOP9 links:

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]

CIDEB links:

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]

LTB4R2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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 rank	MANE	Protein	UniProt
NOP9	NM_174913.3 link	c.*2043T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1	Q86U38-1
CIDEB	NM_001393339.1 link	c.186+233A>G		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 link	c.*2043T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3		Q86U38-1
CIDEB	ENST00000554411.6 link	c.186+233A>G		intron_variant	Intron 2 of 4	1	NM_001393339.1	ENSP00000451089.1		Q9UHD4

Frequencies

GnomAD3 genomes

AF:

0.943

AC:

143440

AN:

152138

Hom.:

67695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.913

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.963

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.946

GnomAD4 exome

AF:

0.951

AC:

245306

AN:

257910

Hom.:

116815

Cov.:

AF XY:

0.952

AC XY:

126225

AN XY:

132604

show subpopulations

Gnomad4 AFR exome

AF:

0.910

Gnomad4 AMR exome

AF:

0.932

Gnomad4 ASJ exome

AF:

0.958

Gnomad4 EAS exome

AF:

0.850

Gnomad4 SAS exome

AF:

0.954

Gnomad4 FIN exome

AF:

0.973

Gnomad4 NFE exome

AF:

0.964

Gnomad4 OTH exome

AF:

0.952

GnomAD4 genome

AF:

0.943

AC:

143535

AN:

152256

Hom.:

67733

Cov.:

AF XY:

0.942

AC XY:

70145

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.912

Gnomad4 AMR

AF:

0.932

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:

0.947

Alfa

AF:

0.959

Hom.:

65131

Bravo

AF:

0.938

Asia WGS

AF:

0.912

AC:

3173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

5.0

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over