14-24316327-A-G

Position:

• chr14-24316327-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001143919.3(LTB4R):​c.676A>G​(p.Ile226Val) 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. 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: 2.65

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3341258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R	NM_001143919.3	c.676A>G	p.Ile226Val	missense_variant	2/2	ENST00000345363.8
LTB4R	NM_181657.3	c.676A>G	p.Ile226Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTB4R	ENST00000345363.8	c.676A>G	p.Ile226Val	missense_variant	2/2	1	NM_001143919.3	P1
LTB4R	ENST00000396782.2	c.676A>G	p.Ile226Val	missense_variant	2/2	1		P1
LTB4R	ENST00000396789.4	c.676A>G	p.Ile226Val	missense_variant	2/2	1		P1
LTB4R	ENST00000556141.1	c.376A>G	p.Ile126Val	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

Dec 01, 2022

The c.676A>G (p.I226V) alteration is located in exon 2 (coding exon 1) of the LTB4R gene. This alteration results from a A to G substitution at nucleotide position 676, causing the isoleucine (I) at amino acid position 226 to be replaced by a valine (V). 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	0.33
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.38	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.11	T;T;D;T
Sift4G	Uncertain	0.023	D;D;T;D
Polyphen		0.99	D;D;.;D
Vest4		0.32
MutPred		0.47		Gain of MoRF binding (P = 0.1102);Gain of MoRF binding (P = 0.1102);.;Gain of MoRF binding (P = 0.1102);
MVP		0.30
MPC		1.7
ClinPred		0.86	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.25

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: chr14-24785533;