14-24311721-G-C

Position:

• chr14-24311721-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019839.5(LTB4R2):​c.1057G>C​(p.Gly353Arg) 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. 16/21 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: LTB4R2 NM_019839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.221

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]

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05820045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R2	NM_019839.5	c.1057G>C	p.Gly353Arg	missense_variant	2/2	ENST00000533293.2
LTB4R	NM_001143919.3	c.-99G>C		5_prime_UTR_variant	1/2	ENST00000345363.8
LTB4R2	NM_001164692.3	c.1057G>C	p.Gly353Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTB4R2	ENST00000533293.2	c.1057G>C	p.Gly353Arg	missense_variant	2/2	1	NM_019839.5	P1
LTB4R	ENST00000345363.8	c.-99G>C		5_prime_UTR_variant	1/2	1	NM_001143919.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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 19, 2023

The c.1057G>C (p.G353R) alteration is located in exon 2 (coding exon 1) of the LTB4R2 gene. This alteration results from a G to C substitution at nucleotide position 1057, causing the glycine (G) at amino acid position 353 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	Benign	0.069
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.019	B;.;.
Vest4		0.056
MutPred		0.29		Gain of solvent accessibility (P = 0.0456);.;.;
MVP		0.54
MPC		0.67
ClinPred		0.17	T
GERP RS		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.10
gMVP		0.28

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: chr14-24780927;