14-24316292-G-A

Position:

• chr14-24316292-G-A

Variant summary

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

The NM_001143919.3(LTB4R):​c.641G>A​(p.Arg214His) 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 benign outcome for this variant. 12/21 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)
• Consequence: LTB4R NM_001143919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.988

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=0.11626792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R	NM_001143919.3	c.641G>A	p.Arg214His	missense_variant	2/2	ENST00000345363.8
LTB4R	NM_181657.3	c.641G>A	p.Arg214His	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTB4R	ENST00000345363.8	c.641G>A	p.Arg214His	missense_variant	2/2	1	NM_001143919.3	P1
LTB4R	ENST00000396782.2	c.641G>A	p.Arg214His	missense_variant	2/2	1		P1
LTB4R	ENST00000396789.4	c.641G>A	p.Arg214His	missense_variant	2/2	1		P1
LTB4R	ENST00000556141.1	c.341G>A	p.Arg114His	missense_variant	2/2	3

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

Jan 22, 2024

The c.641G>A (p.R214H) alteration is located in exon 2 (coding exon 1) of the LTB4R gene. This alteration results from a G to A substitution at nucleotide position 641, causing the arginine (R) at amino acid position 214 to be replaced by a histidine (H). 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	0.091
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M;M;.;M
MutationTaster	Benign	0.64	N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.042	D;D;D;D
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.27	B;B;.;B
Vest4		0.13
MutPred		0.43		Loss of methylation at R214 (P = 0.0283);Loss of methylation at R214 (P = 0.0283);.;Loss of methylation at R214 (P = 0.0283);
MVP		0.54
MPC		1.1
ClinPred		0.61	D
GERP RS		3.8
Varity_R		0.084
gMVP		0.53

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: rs751311323; hg19: chr14-24785498;