Variant 14-24316262-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001143919.3(LTB4R):c.611T>C(p.Ile204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LTB4R
NM_001143919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTB4R	NM_001143919.3 linkuse as main transcript	c.611T>C	p.Ile204Thr	missense_variant	2/2	ENST00000345363.8
LTB4R	NM_181657.3 linkuse as main transcript	c.611T>C	p.Ile204Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LTB4R	ENST00000345363.8 linkuse as main transcript	c.611T>C	p.Ile204Thr	missense_variant	2/2	1	NM_001143919.3	P1
LTB4R	ENST00000396782.2 linkuse as main transcript	c.611T>C	p.Ile204Thr	missense_variant	2/2	1		P1
LTB4R	ENST00000396789.4 linkuse as main transcript	c.611T>C	p.Ile204Thr	missense_variant	2/2	1		P1
LTB4R	ENST00000556141.1 linkuse as main transcript	c.311T>C	p.Ile104Thr	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460186

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726410

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 24, 2024

The c.611T>C (p.I204T) alteration is located in exon 2 (coding exon 1) of the LTB4R gene. This alteration results from a T to C substitution at nucleotide position 611, causing the isoleucine (I) at amino acid position 204 to be replaced by a threonine (T). 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

0.32

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;.;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.94

D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.28

T;T;T;T

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.90

P;P;.;P

Vest4

0.79

MutPred

0.88

Gain of disorder (P = 0.01);Gain of disorder (P = 0.01);.;Gain of disorder (P = 0.01);

MVP

0.88

MPC

2.1

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over