rs2144493

Variant names:

• chr14-24305411-C-A
• rs2144493
• NM_174913.3:c.*316C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-24305411-C-A
• chr14-24305411-C-G
• chr14-24305411-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174913.3(NOP9):​c.*316C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOP9 NM_174913.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 5 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP9	NM_174913.3	c.*316C>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000267425.8	NP_777573.1
CIDEB	NM_001393339.1	c.*222G>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000554411.6	NP_001380268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.*316C>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_174913.3	ENSP00000267425.3
CIDEB	ENST00000554411.6	c.*222G>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001393339.1	ENSP00000451089.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000220 AC: 1 AN: 454660 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 234272

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12042

American (AMR) AF: 0.00 AC: 0 AN: 12366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12836

East Asian (EAS) AF: 0.00 AC: 0 AN: 27926

South Asian (SAS) AF: 0.00 AC: 0 AN: 32448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1970

European-Non Finnish (NFE) AF: 0.00000331 AC: 1 AN: 302192

Other (OTH) AF: 0.00 AC: 0 AN: 25302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 87484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.18
PromoterAI		-0.017	Neutral

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: rs2144493; hg19: chr14-24774617;