14-24315857-T-G

Position:

• chr14-24315857-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001143919.3(LTB4R):​c.206T>G​(p.Leu69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LTB4R NM_001143919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

LTB4R (HGNC:6713): (leukotriene B4 receptor) 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 signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R	NM_001143919.3	c.206T>G	p.Leu69Arg	missense_variant	2/2	ENST00000345363.8
LTB4R	NM_181657.3	c.206T>G	p.Leu69Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTB4R	ENST00000345363.8	c.206T>G	p.Leu69Arg	missense_variant	2/2	1	NM_001143919.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Apr 29, 2024

The c.206T>G (p.L69R) alteration is located in exon 2 (coding exon 1) of the LTB4R gene. This alteration results from a T to G substitution at nucleotide position 206, causing the leucine (L) at amino acid position 69 to be replaced by an arginine (R). 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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;D;D;D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	4.4	.;H;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.9	D;D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	.;D;D;D
Vest4		0.92, 0.94, 0.92
MutPred		0.88		Gain of methylation at L69 (P = 0.0121);Gain of methylation at L69 (P = 0.0121);Gain of methylation at L69 (P = 0.0121);Gain of methylation at L69 (P = 0.0121);
MVP		0.93
MPC		2.4
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.85
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24785063;