Genetic Variant NOP9:c.*316C>T (chr14-24305411-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_174913.3(NOP9):c.*316C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 606,522 control chromosomes in the GnomAD database, including 274,445 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 ( 67750 hom., cov: 29)

Exomes 𝑓: 0.95 ( 206695 hom. )

Consequence

NOP9
NM_174913.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.177

Publications

5 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.*316C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1
CIDEB	NM_001393339.1 link	c.*222G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000554411.6	NP_001380268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8 link	c.*316C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3
CIDEB	ENST00000554411.6 link	c.*222G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001393339.1	ENSP00000451089.1

Frequencies

GnomAD3 genomes

AF:

0.944

AC:

143349

AN:

151924

Hom.:

67704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.963

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.945

GnomAD4 exome

AF:

0.953

AC:

433137

AN:

454480

Hom.:

206695

Cov.:

AF XY:

0.953

AC XY:

223180

AN XY:

234178

show subpopulations

African (AFR)

AF:

0.918

AC:

11049

AN:

12036

American (AMR)

AF:

0.927

AC:

11466

AN:

12366

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

12291

AN:

12830

East Asian (EAS)

AF:

0.830

AC:

23156

AN:

27906

South Asian (SAS)

AF:

0.955

AC:

30959

AN:

32426

European-Finnish (FIN)

AF:

0.973

AC:

26842

AN:

27578

Middle Eastern (MID)

AF:

0.973

AC:

1914

AN:

1968

European-Non Finnish (NFE)

AF:

0.965

AC:

291360

AN:

302074

Other (OTH)

AF:

0.953

AC:

24100

AN:

25296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

949

1898

2846

3795

4744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2442

4884

7326

9768

12210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.944

AC:

143453

AN:

152042

Hom.:

67750

Cov.:

AF XY:

0.943

AC XY:

70085

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.917

AC:

38015

AN:

41460

American (AMR)

AF:

0.929

AC:

14191

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.963

AC:

3342

AN:

3472

East Asian (EAS)

AF:

0.844

AC:

4332

AN:

5132

South Asian (SAS)

AF:

0.948

AC:

4562

AN:

4814

European-Finnish (FIN)

AF:

0.975

AC:

10324

AN:

10588

Middle Eastern (MID)

AF:

0.963

AC:

283

AN:

294

European-Non Finnish (NFE)

AF:

0.964

AC:

65511

AN:

67982

Other (OTH)

AF:

0.946

AC:

1999

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

416

832

1249

1665

2081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.957

Hom.:

87484

Bravo

AF:

0.938

Asia WGS

AF:

0.909

AC:

3163

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.53

PhyloP100

-0.18

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over