14-24307013-T-C

Position:

• chr14-24307013-T-C

Variant summary

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

The ENST00000267425.8(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 ENST00000267425.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*1918T>C		3_prime_UTR_variant	10/10	ENST00000267425.8	NP_777573.1
CIDEB	NM_001393339.1	c.186+358A>G		intron_variant		ENST00000554411.6	NP_001380268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.*1918T>C		3_prime_UTR_variant	10/10	1	NM_174913.3	ENSP00000267425	P1
CIDEB	ENST00000554411.6	c.186+358A>G		intron_variant		1	NM_001393339.1	ENSP00000451089	P1

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

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.129

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

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.119

Alfa AF: 0.114 Hom.: 205

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

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: rs2332320; hg19: chr14-24776219;