14-24316687-C-T

Position:

• chr14-24316687-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143919.3(LTB4R):​c.1036C>T​(p.Leu346Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,385,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: LTB4R NM_001143919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09735957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB4R	NM_001143919.3	c.1036C>T	p.Leu346Phe	missense_variant	2/2	ENST00000345363.8	NP_001137391.1
LTB4R	NM_181657.3	c.1036C>T	p.Leu346Phe	missense_variant	2/2		NP_858043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTB4R	ENST00000345363.8	c.1036C>T	p.Leu346Phe	missense_variant	2/2	1	NM_001143919.3	ENSP00000307445.3
LTB4R	ENST00000396782.2	c.1036C>T	p.Leu346Phe	missense_variant	2/2	1		ENSP00000380002.2
LTB4R	ENST00000396789.4	c.1036C>T	p.Leu346Phe	missense_variant	2/2	1		ENSP00000380008.4
LTB4R	ENST00000556141.1	c.*40C>T		downstream_gene_variant		3		ENSP00000451929.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1385828 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 684742

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: 0.00000186

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.89	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.58	P;P;P
Vest4		0.084
MutPred		0.044		Gain of methylation at K347 (P = 0.0284);Gain of methylation at K347 (P = 0.0284);Gain of methylation at K347 (P = 0.0284);
MVP		0.44
MPC		2.0
ClinPred		0.10	T
GERP RS		2.4
Varity_R		0.045
gMVP		0.14

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: rs17849864; hg19: chr14-24785893;