14-24308385-C-G

Variant names:

• chr14-24308385-C-G
• rs2180197
• NM_174913.3:c.*3290C>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.*3290C>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 0.94 in 194,966 control chromosomes in the GnomAD database, including 86,329 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 0.94 (66739 hom., cov: 29)
  • Exomes 𝑓: 0.96 (19590 hom.)
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.958 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.*3290C>G		3_prime_UTR	Exon 10 of 10	NP_777573.1	Q86U38-1
	NOP9	NM_001286367.2		c.*3427C>G		3_prime_UTR	Exon 10 of 10	NP_001273296.1	Q86U38-2
	CIDEB	NM_001318807.3		c.-63+94G>C		intron	N/A	NP_001305736.1	Q9UHD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.*3290C>G		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3	Q86U38-1
	CIDEB	ENST00000258807.5	TSL:1	c.-63+94G>C		intron	N/A	ENSP00000258807.5	Q9UHD4
	CIDEB	ENST00000967605.1		c.-527G>C		5_prime_UTR	Exon 1 of 5	ENSP00000637664.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142251 AN: 151930 Hom.: 66708 Cov.: 29

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.942

GnomAD4 exome AF: 0.955 AC: 40987 AN: 42918 Hom.: 19590 Cov.: 0 AF XY: 0.955 AC XY: 21787 AN XY: 22820

African (AFR) AF: 0.905 AC: 1235 AN: 1364

American (AMR) AF: 0.941 AC: 3360 AN: 3572

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 789 AN: 818

East Asian (EAS) AF: 0.864 AC: 2420 AN: 2800

South Asian (SAS) AF: 0.958 AC: 6389 AN: 6672

European-Finnish (FIN) AF: 0.974 AC: 1126 AN: 1156

Middle Eastern (MID) AF: 0.963 AC: 104 AN: 108

European-Non Finnish (NFE) AF: 0.969 AC: 23764 AN: 24536

Other (OTH) AF: 0.951 AC: 1800 AN: 1892

GnomAD4 genome AF: 0.936 AC: 142337 AN: 152048 Hom.: 66739 Cov.: 29 AF XY: 0.935 AC XY: 69540 AN XY: 74336

African (AFR) AF: 0.890 AC: 36848 AN: 41420

American (AMR) AF: 0.929 AC: 14190 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3340 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4376 AN: 5152

South Asian (SAS) AF: 0.947 AC: 4564 AN: 4820

European-Finnish (FIN) AF: 0.975 AC: 10331 AN: 10596

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65521 AN: 67990

Other (OTH) AF: 0.943 AC: 1991 AN: 2112

Alfa AF: 0.947 Hom.: 8478

Bravo AF: 0.930

Asia WGS AF: 0.901 AC: 3134 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	1.8
DANN	Benign	0.67
PhyloP100		0.076
PromoterAI		-0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2180197; hg19: chr14-24777591;