rs1950504

Variant names:

• chr14-24311158-A-G
• rs1950504
• NM_019839.5:c.494A>G

Variant summary

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

The NM_019839.5(LTB4R2):​c.494A>G​(p.Asp165Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00692 in 1,602,994 control chromosomes in the GnomAD database, including 717 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (365 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (352 hom.)
• Consequence: LTB4R2 NM_019839.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001957804).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB4R2	NM_019839.5	c.494A>G	p.Asp165Gly	missense_variant	Exon 2 of 2	ENST00000533293.2	NP_062813.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTB4R2	ENST00000533293.2	c.494A>G	p.Asp165Gly	missense_variant	Exon 2 of 2	1	NM_019839.5	ENSP00000433290.1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5727 AN: 152128 Hom.: 364 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.00767 AC: 1698 AN: 221512 Hom.: 94 AF XY: 0.00564 AC XY: 688 AN XY: 121886

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00439

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000174

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00454

GnomAD4 exome AF: 0.00369 AC: 5352 AN: 1450758 Hom.: 352 Cov.: 31 AF XY: 0.00312 AC XY: 2254 AN XY: 721282

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000686

Gnomad4 OTH exome AF: 0.00778

GnomAD4 genome AF: 0.0377 AC: 5737 AN: 152236 Hom.: 365 Cov.: 33 AF XY: 0.0364 AC XY: 2706 AN XY: 74432

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00965 Hom.: 24

Bravo AF: 0.0423

ESP6500AA AF: 0.103 AC: 450

ESP6500EA AF: 0.000235 AC: 2

ExAC AF: 0.00965 AC: 1151

Asia WGS AF: 0.00810 AC: 29 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.3
DANN	Benign	0.89
DEOGEN2	Benign	0.061	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
MetaRNN	Benign	0.0020	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.079
MVP		0.56
MPC		0.70
ClinPred		0.0031	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.48

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: rs1950504; hg19: chr14-24780364;