14-24305411-C-T

Position:

• chr14-24305411-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CIDEB	NM_001393339.1	c.*222G>A		3_prime_UTR_variant	5/5	ENST00000554411.6	NP_001380268.1
NOP9	NM_174913.3	c.*316C>T		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.*316C>T		3_prime_UTR_variant	10/10	1	NM_174913.3	ENSP00000267425	P1
CIDEB	ENST00000554411.6	c.*222G>A		3_prime_UTR_variant	5/5	1	NM_001393339.1	ENSP00000451089	P1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143349 AN: 151924 Hom.: 67704 Cov.: 29

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.: 6 AF XY: 0.953 AC XY: 223180 AN XY: 234178

Gnomad4 AFR exome AF: 0.918

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.958

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.973

Gnomad4 NFE exome AF: 0.965

Gnomad4 OTH exome AF: 0.953

GnomAD4 genome AF: 0.944 AC: 143453 AN: 152042 Hom.: 67750 Cov.: 29 AF XY: 0.943 AC XY: 70085 AN XY: 74324

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.946

Alfa AF: 0.959 Hom.: 66955

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
DANN	Benign	0.53
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: rs2144493; hg19: chr14-24774617; COSMIC: COSV51864701; COSMIC: COSV51864701;