14-24307251-C-G

Variant names:

• chr14-24307251-C-G
• rs11158634
• NM_174913.3:c.*2156C>G

Variant summary

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

The NM_174913.3(NOP9):​c.*2156C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,114,768 control chromosomes in the GnomAD database, including 22,626 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 (3001 hom., cov: 32)
  • Exomes 𝑓: 0.19 (19625 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 8 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	NM_174913.3	MANE Select	c.*2156C>G		3_prime_UTR	Exon 10 of 10	NP_777573.1	Q86U38-1
	CIDEB	NM_001393339.1	MANE Select	c.186+120G>C		intron	N/A	NP_001380268.1	Q9UHD4
	NOP9	NM_001286367.2		c.*2293C>G		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.*2156C>G		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3	Q86U38-1
	CIDEB	ENST00000554411.6	TSL:1 MANE Select	c.186+120G>C		intron	N/A	ENSP00000451089.1	Q9UHD4
	CIDEB	ENST00000258807.5	TSL:1	c.186+120G>C		intron	N/A	ENSP00000258807.5	Q9UHD4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28415 AN: 152098 Hom.: 3000 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.192 AC: 184441 AN: 962552 Hom.: 19625 Cov.: 13 AF XY: 0.188 AC XY: 91319 AN XY: 485318

African (AFR) AF: 0.166 AC: 3711 AN: 22388

American (AMR) AF: 0.363 AC: 10115 AN: 27856

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 3381 AN: 17376

East Asian (EAS) AF: 0.000735 AC: 27 AN: 36730

South Asian (SAS) AF: 0.112 AC: 6889 AN: 61504

European-Finnish (FIN) AF: 0.142 AC: 6924 AN: 48762

Middle Eastern (MID) AF: 0.118 AC: 346 AN: 2924

European-Non Finnish (NFE) AF: 0.207 AC: 145228 AN: 702312

Other (OTH) AF: 0.183 AC: 7820 AN: 42700

GnomAD4 genome AF: 0.187 AC: 28428 AN: 152216 Hom.: 3001 Cov.: 32 AF XY: 0.182 AC XY: 13509 AN XY: 74422

African (AFR) AF: 0.168 AC: 6984 AN: 41530

American (AMR) AF: 0.287 AC: 4391 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.106 AC: 509 AN: 4824

European-Finnish (FIN) AF: 0.132 AC: 1395 AN: 10598

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

European-Non Finnish (NFE) AF: 0.205 AC: 13955 AN: 68006

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.0948 Hom.: 155

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	1.7
DANN	Benign	0.50
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11158634; hg19: chr14-24776457;