14-24307013-T-C

Variant names:

• chr14-24307013-T-C
• rs2332320
• NM_174913.3:c.*1918T>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.*1918T>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 0.139 in 249,348 control chromosomes in the GnomAD database, including 3,851 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 0.13 (1875 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1976 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*1918T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1
CIDEB	NM_001393339.1	c.186+358A>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	c.*1918T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3
CIDEB	ENST00000554411.6	c.186+358A>G		intron_variant	Intron 2 of 4	1	NM_001393339.1	ENSP00000451089.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19795 AN: 152068 Hom.: 1879 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.154 AC: 14934 AN: 97162 Hom.: 1976 Cov.: 0 AF XY: 0.156 AC XY: 7850 AN XY: 50446

African (AFR) AF: 0.0612 AC: 207 AN: 3380

American (AMR) AF: 0.151 AC: 759 AN: 5030

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 453 AN: 3218

East Asian (EAS) AF: 0.588 AC: 3394 AN: 5772

South Asian (SAS) AF: 0.240 AC: 2070 AN: 8614

European-Finnish (FIN) AF: 0.180 AC: 854 AN: 4750

Middle Eastern (MID) AF: 0.0936 AC: 44 AN: 470

European-Non Finnish (NFE) AF: 0.107 AC: 6395 AN: 60040

Other (OTH) AF: 0.129 AC: 758 AN: 5888

GnomAD4 genome AF: 0.130 AC: 19779 AN: 152186 Hom.: 1875 Cov.: 32 AF XY: 0.139 AC XY: 10379 AN XY: 74412

African (AFR) AF: 0.0804 AC: 3340 AN: 41532

American (AMR) AF: 0.130 AC: 1990 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2733 AN: 5166

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4822

European-Finnish (FIN) AF: 0.191 AC: 2025 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7487 AN: 67984

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.115 Hom.: 363

Bravo AF: 0.124

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		-0.11
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: rs2332320; hg19: chr14-24776219;