rs2516564

chr14-24309437-C-T

Variant summary

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

The ENST00000258807.5(CIDEB):c.-414-607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,200 control chromosomes in the GnomAD database, including 2,932 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 0.18 (2932 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: CIDEB ENST00000258807.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIDEB	NM_001393334.1	c.-1021G>A		5_prime_UTR_variant	2/7
CIDEB	NM_001318807.3	c.-414-607G>A		intron_variant
CIDEB	NM_001393335.1	c.-447-607G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIDEB	ENST00000258807.5	c.-414-607G>A		intron_variant		1		P1
LTB4R2	ENST00000528054.1	c.-1135C>T		5_prime_UTR_variant	1/1
CIDEB	ENST00000336557.9	c.-414-607G>A		intron_variant		2		P1
LTB4R2	ENST00000527924.6	c.-95-734C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27967 AN: 152028 Hom.: 2931 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.148 AC: 8 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.156 AC XY: 5 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.184 AC: 27980 AN: 152146 Hom.: 2932 Cov.: 32 AF XY: 0.179 AC XY: 13276 AN XY: 74374

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.186

Alfa AF: 0.194 Hom.: 480

Bravo AF: 0.195

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.4
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2516564; hg19: chr14-24778643;