chr14-24316687-C-G

Variant names:

• chr14-24316687-C-G
• rs17849864
• NM_001143919.3:c.1036C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001143919.3(LTB4R):​c.1036C>G​(p.Leu346Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,385,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LTB4R NM_001143919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0630905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTB4R	NM_001143919.3	MANE Select	c.1036C>G	p.Leu346Val	missense	Exon 2 of 2	NP_001137391.1
	LTB4R	NM_181657.3		c.1036C>G	p.Leu346Val	missense	Exon 2 of 2	NP_858043.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTB4R	ENST00000345363.8	TSL:1 MANE Select	c.1036C>G	p.Leu346Val	missense	Exon 2 of 2	ENSP00000307445.3
	LTB4R	ENST00000396782.2	TSL:1	c.1036C>G	p.Leu346Val	missense	Exon 2 of 2	ENSP00000380002.2
	LTB4R	ENST00000396789.4	TSL:1	c.1036C>G	p.Leu346Val	missense	Exon 2 of 2	ENSP00000380008.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1385828 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 2 AN XY: 684742

African (AFR) AF: 0.00 AC: 0 AN: 29292

American (AMR) AF: 0.00 AC: 0 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24558

East Asian (EAS) AF: 0.00 AC: 0 AN: 33510

South Asian (SAS) AF: 0.00 AC: 0 AN: 78894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1074990

Other (OTH) AF: 0.00 AC: 0 AN: 57274

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.10
Sift	Benign	0.36	T
Sift4G	Uncertain	0.038	D
Polyphen		0.075	B
Vest4		0.11
MutPred		0.088		Gain of methylation at K347 (P = 0.0367)
MVP		0.43
MPC		1.7
ClinPred		0.096	T
GERP RS		2.4
Varity_R		0.033
gMVP		0.19
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs17849864; hg19: chr14-24785893;