rs11158635

Variant names:

• chr14-24307563-G-T
• rs11158635
• NM_174913.3:c.*2468G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	NM_174913.3	MANE Select	c.*2468G>T		3_prime_UTR	Exon 10 of 10	NP_777573.1
	CIDEB	NM_001393339.1	MANE Select	c.42-48C>A		intron	N/A	NP_001380268.1
	NOP9	NM_001286367.2		c.*2605G>T		3_prime_UTR	Exon 10 of 10	NP_001273296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.*2468G>T		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3
	CIDEB	ENST00000554411.6	TSL:1 MANE Select	c.42-48C>A		intron	N/A	ENSP00000451089.1
	CIDEB	ENST00000258807.5	TSL:1	c.42-48C>A		intron	N/A	ENSP00000258807.5

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

GnomAD2 exomes AF: 0.192 AC: 45427 AN: 237054 AF XY: 0.183

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 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

African (AFR) AF: 0.165 AC: 5474 AN: 33122

American (AMR) AF: 0.373 AC: 16329 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 4852 AN: 24680

East Asian (EAS) AF: 0.000785 AC: 31 AN: 39470

South Asian (SAS) AF: 0.113 AC: 9414 AN: 83258

European-Finnish (FIN) AF: 0.142 AC: 7469 AN: 52644

Middle Eastern (MID) AF: 0.117 AC: 661 AN: 5672

European-Non Finnish (NFE) AF: 0.208 AC: 228581 AN: 1098034

Other (OTH) AF: 0.184 AC: 10956 AN: 59484

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

African (AFR) AF: 0.168 AC: 6939 AN: 41414

American (AMR) AF: 0.287 AC: 4371 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5158

South Asian (SAS) AF: 0.106 AC: 507 AN: 4802

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13931 AN: 67956

Other (OTH) AF: 0.185 AC: 388 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.65
PhyloP100		0.44
BranchPoint Hunter		1.0
PromoterAI		0.025	Neutral
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: rs11158635; hg19: chr14-24776769;