Variant chr14-24316330-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001143919.3(LTB4R):c.679A>G(p.Ile227Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,447,236 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LTB4R
NM_001143919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

Variant links:

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]

LTB4R links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09665775).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R	NM_001143919.3 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	2/2	ENST00000345363.8
LTB4R	NM_181657.3 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LTB4R	ENST00000345363.8 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	2/2	1	NM_001143919.3	P1
LTB4R	ENST00000396782.2 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	2/2	1		P1
LTB4R	ENST00000396789.4 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	2/2	1		P1
LTB4R	ENST00000556141.1 linkuse as main transcript	c.379A>G	p.Ile127Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

231056

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1447236

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719370

show subpopulations

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:

0.00000813

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000836

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.679A>G (p.I227V) 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 679, causing the isoleucine (I) at amino acid position 227 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

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.081

T;T;.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.16

M_CAP

Benign

0.046

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.10

N;N;.;N

MutationTaster

Benign

0.73

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.15

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.86

T;T;T;T

Sift4G

Benign

0.66

T;T;T;T

Polyphen

0.17

B;B;.;B

Vest4

0.21

MutPred

0.45

Gain of catalytic residue at I227 (P = 0.0196);Gain of catalytic residue at I227 (P = 0.0196);.;Gain of catalytic residue at I227 (P = 0.0196);

MVP

0.68

MPC

0.76

ClinPred

0.15

GERP RS

4.5

Varity_R

0.039

gMVP

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over