rs11158635

Positions:

• chr14-24307563-G-T

Variant summary

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

The NM_174913.3(NOP9):​c.*2468G>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 0.196 in 1,592,022 control chromosomes in the GnomAD database, including 33,480 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 0.19 (2984 hom., cov: 31)
  • Exomes 𝑓: 0.20 (30496 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP9	NM_174913.3	c.*2468G>T		3_prime_UTR_variant	10/10	ENST00000267425.8
CIDEB	NM_001393339.1	c.42-48C>A		intron_variant		ENST00000554411.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP9	ENST00000267425.8	c.*2468G>T		3_prime_UTR_variant	10/10	1	NM_174913.3	P1
CIDEB	ENST00000554411.6	c.42-48C>A		intron_variant		1	NM_001393339.1	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28318 AN: 151808 Hom.: 2983 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.192 AC: 45427 AN: 237054 Hom.: 5562 AF XY: 0.183 AC XY: 23288 AN XY: 127540

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.00158

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.197 AC: 283767 AN: 1440098 Hom.: 30496 Cov.: 31 AF XY: 0.193 AC XY: 138264 AN XY: 714738

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.000785

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.186 AC: 28330 AN: 151924 Hom.: 2984 Cov.: 31 AF XY: 0.181 AC XY: 13456 AN XY: 74240

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.185

Alfa AF: 0.192 Hom.: 561

Bravo AF: 0.199

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.65
BranchPoint Hunter		1.0

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: rs11158635; hg19: chr14-24776769;