14-24307825-A-G

Variant names:

• chr14-24307825-A-G
• rs761940963
• NM_001393339.1:c.34T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001393339.1(CIDEB):​c.34T>C​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CIDEB NM_001393339.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942
• Publications: 0 publications found

Genes affected

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]

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]

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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.942 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393339.1. 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
	CIDEB	NM_001393339.1	MANE Select	c.34T>C	p.Leu12Leu	synonymous	Exon 1 of 5	NP_001380268.1	Q9UHD4
	NOP9	NM_174913.3	MANE Select	c.*2730A>G		3_prime_UTR	Exon 10 of 10	NP_777573.1	Q86U38-1
	CIDEB	NM_001318807.3		c.34T>C	p.Leu12Leu	synonymous	Exon 4 of 8	NP_001305736.1	Q9UHD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEB	ENST00000554411.6	TSL:1 MANE Select	c.34T>C	p.Leu12Leu	synonymous	Exon 1 of 5	ENSP00000451089.1	Q9UHD4
	CIDEB	ENST00000258807.5	TSL:1	c.34T>C	p.Leu12Leu	synonymous	Exon 3 of 7	ENSP00000258807.5	Q9UHD4
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.*2730A>G		3_prime_UTR	Exon 10 of 10	ENSP00000267425.3	Q86U38-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 220422 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443422 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716048

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 41792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 39136

South Asian (SAS) AF: 0.00 AC: 0 AN: 83206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102760

Other (OTH) AF: 0.00 AC: 0 AN: 59716

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.3
DANN	Benign	0.83
PhyloP100		0.94
PromoterAI		0.061	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: rs761940963; hg19: chr14-24777031;