rs2748543

Positions:

• chr14-24309468-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000258807.5(CIDEB):​c.-414-638G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,280 control chromosomes in the GnomAD database, including 2,367 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 0.15 (2366 hom., cov: 32)
  • Exomes 𝑓: 0.082 (1 hom.)
• Consequence: CIDEB ENST00000258807.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEB	NM_001393334.1	c.-1052G>T		5_prime_UTR_variant	2/7		NP_001380263.1
CIDEB	NM_001318807.3	c.-414-638G>T		intron_variant			NP_001305736.1
CIDEB	NM_001393335.1	c.-447-638G>T		intron_variant			NP_001380264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIDEB	ENST00000258807.5	c.-414-638G>T		intron_variant		1		ENSP00000258807	P1
LTB4R2	ENST00000528054.1	c.-1104C>A		5_prime_UTR_variant	1/1			ENSP00000432146
CIDEB	ENST00000336557.9	c.-414-638G>T		intron_variant		2		ENSP00000337731	P1
LTB4R2	ENST00000527924.6	c.-95-703C>A		intron_variant		3		ENSP00000436668

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22852 AN: 152052 Hom.: 2365 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.0818 AC: 9 AN: 110 Hom.: 1 Cov.: 0 AF XY: 0.0972 AC XY: 7 AN XY: 72

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.150 AC: 22857 AN: 152170 Hom.: 2366 Cov.: 32 AF XY: 0.147 AC XY: 10914 AN XY: 74384

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.162

Alfa AF: 0.184 Hom.: 580

Bravo AF: 0.156

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2748543; hg19: chr14-24778674;