14-24311508-A-T

Position:

chr14-24311508-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143919.3(LTB4R):c.-312A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LTB4R
NM_001143919.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

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]

LTB4R2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20907113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB4R	NM_001143919.3 linkuse as main transcript	c.-312A>T		5_prime_UTR_premature_start_codon_gain_variant	1/2	ENST00000345363.8	NP_001137391.1	Q15722
LTB4R2	NM_019839.5 linkuse as main transcript	c.844A>T	p.Ser282Cys	missense_variant	2/2	ENST00000533293.2	NP_062813.2	Q9NPC1B4E292
LTB4R	NM_001143919.3 linkuse as main transcript	c.-312A>T		5_prime_UTR_variant	1/2	ENST00000345363.8	NP_001137391.1	Q15722
LTB4R2	NM_001164692.3 linkuse as main transcript	c.844A>T	p.Ser282Cys	missense_variant	2/2		NP_001158164.1	Q9NPC1B4E292

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LTB4R	ENST00000345363.8 linkuse as main transcript	c.-312A>T		5_prime_UTR_premature_start_codon_gain_variant	1/2	1	NM_001143919.3	ENSP00000307445.3	Q15722
LTB4R2	ENST00000533293.2 linkuse as main transcript	c.844A>T	p.Ser282Cys	missense_variant	2/2	1	NM_019839.5	ENSP00000433290.1	Q9NPC1
LTB4R	ENST00000345363.8 linkuse as main transcript	c.-312A>T		5_prime_UTR_variant	1/2	1	NM_001143919.3	ENSP00000307445.3	Q15722

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000831

AC:

AN:

240664

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131028

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1450252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721976

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Aug 04, 2024

The c.844A>T (p.S282C) alteration is located in exon 2 (coding exon 1) of the LTB4R2 gene. This alteration results from a A to T substitution at nucleotide position 844, causing the serine (S) at amino acid position 282 to be replaced by a cysteine (C). 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

0.16

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.052

T;.;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.56

M_CAP

Benign

0.021

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.33

N;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.19

T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.11

B;.;.;.

Vest4

0.22

MutPred

0.59

Loss of glycosylation at S313 (P = 0.1456);.;.;.;

MVP

0.58

MPC

1.5

ClinPred

0.29

GERP RS

4.8

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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