14-24307138-T-C

Variant names:

• chr14-24307138-T-C
• rs1053648
• NM_174913.3:c.*2043T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174913.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	NM_174913.3	MANE Select	c.*2043T>C		3_prime_UTR	Exon 10 of 10	NP_777573.1	Q86U38-1
	CIDEB	NM_001393339.1	MANE Select	c.186+233A>G		intron	N/A	NP_001380268.1	Q9UHD4
	NOP9	NM_001286367.2		c.*2180T>C		3_prime_UTR	Exon 10 of 10	NP_001273296.1	Q86U38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.*2043T>C		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3	Q86U38-1
	CIDEB	ENST00000554411.6	TSL:1 MANE Select	c.186+233A>G		intron	N/A	ENSP00000451089.1	Q9UHD4
	CIDEB	ENST00000258807.5	TSL:1	c.186+233A>G		intron	N/A	ENSP00000258807.5	Q9UHD4

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143440 AN: 152138 Hom.: 67695 Cov.: 32

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.: 4 AF XY: 0.952 AC XY: 126225 AN XY: 132604

African (AFR) AF: 0.910 AC: 6820 AN: 7492

American (AMR) AF: 0.932 AC: 8927 AN: 9580

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 8732 AN: 9112

East Asian (EAS) AF: 0.850 AC: 18679 AN: 21966

South Asian (SAS) AF: 0.954 AC: 10282 AN: 10780

European-Finnish (FIN) AF: 0.973 AC: 19198 AN: 19736

Middle Eastern (MID) AF: 0.975 AC: 1244 AN: 1276

European-Non Finnish (NFE) AF: 0.964 AC: 155842 AN: 161608

Other (OTH) AF: 0.952 AC: 15582 AN: 16360

GnomAD4 genome AF: 0.943 AC: 143535 AN: 152256 Hom.: 67733 Cov.: 32 AF XY: 0.942 AC XY: 70145 AN XY: 74446

African (AFR) AF: 0.912 AC: 37885 AN: 41518

American (AMR) AF: 0.932 AC: 14256 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3340 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4397 AN: 5178

South Asian (SAS) AF: 0.947 AC: 4565 AN: 4818

European-Finnish (FIN) AF: 0.975 AC: 10351 AN: 10616

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65564 AN: 68036

Other (OTH) AF: 0.947 AC: 2000 AN: 2112

Alfa AF: 0.959 Hom.: 78263

Bravo AF: 0.938

Asia WGS AF: 0.912 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.0
DANN	Benign	0.43
PhyloP100		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1053648; hg19: chr14-24776344;