14-24310819-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019839.5(LTB4R2):c.155G>A(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LTB4R2 NM_019839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.280

Genes affected

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]

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28216463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R2	NM_019839.5	c.155G>A	p.Arg52Gln	missense_variant	2/2	ENST00000533293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTB4R2	ENST00000533293.2	c.155G>A	p.Arg52Gln	missense_variant	2/2	1	NM_019839.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1442760 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.155G>A (p.R52Q) alteration is located in exon 2 (coding exon 1) of the LTB4R2 gene. This alteration results from a G to A substitution at nucleotide position 155, causing the arginine (R) at amino acid position 52 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.035	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.30	T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.014	.;B;.;.;.
Vest4		0.052, 0.055, 0.053
MutPred		0.80		.;Loss of methylation at R83 (P = 0.0289);.;.;.;
MVP		0.57
MPC		0.62
ClinPred		0.25	T
GERP RS		2.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.3
Varity_R		0.084
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1251176798; hg19: chr14-24780025; COSMIC: COSV99350894; COSMIC: COSV99350894;