Genetic Variant LTB4R2:c.-11+133T>G (chr14-24310388-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019839.5(LTB4R2):c.-11+133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 616,996 control chromosomes in the GnomAD database, including 278,907 homozygotes. 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: 𝑓 0.94 ( 67701 hom., cov: 30)

Exomes 𝑓: 0.95 ( 211206 hom. )

Consequence

LTB4R2
NM_019839.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.234

Publications

10 publications found

Variant links:

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]

LTB4R2 links:

CIDEB (HGNC:1977): (cell death inducing DFFA like effector b) Enables identical protein binding activity. Involved in activation of cysteine-type endopeptidase activity; positive regulation of cell death; and positive regulation of release of cytochrome c from mitochondria. Acts upstream of or within apoptotic process. Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CIDEB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB4R2	NM_019839.5 link	c.-11+133T>G		intron_variant	Intron 1 of 1	ENST00000533293.2	NP_062813.2	Q9NPC1B4E292

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTB4R2	ENST00000533293.2 link	c.-11+133T>G		intron_variant	Intron 1 of 1	1	NM_019839.5	ENSP00000433290.1		Q9NPC1

Frequencies

GnomAD3 genomes

AF:

0.943

AC:

143360

AN:

152030

Hom.:

67663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.913

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.963

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.945

GnomAD4 exome

AF:

0.953

AC:

442906

AN:

464848

Hom.:

211206

Cov.:

AF XY:

0.953

AC XY:

235457

AN XY:

247060

show subpopulations

African (AFR)

AF:

0.913

AC:

11603

AN:

12702

American (AMR)

AF:

0.932

AC:

18698

AN:

20052

Ashkenazi Jewish (ASJ)

AF:

0.957

AC:

13942

AN:

14570

East Asian (EAS)

AF:

0.852

AC:

26773

AN:

31430

South Asian (SAS)

AF:

0.954

AC:

45740

AN:

47948

European-Finnish (FIN)

AF:

0.973

AC:

29840

AN:

30662

Middle Eastern (MID)

AF:

0.973

AC:

2041

AN:

2098

European-Non Finnish (NFE)

AF:

0.965

AC:

268656

AN:

278510

Other (OTH)

AF:

0.953

AC:

25613

AN:

26876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1200

2401

3601

4802

6002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

926

1852

2778

3704

4630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.943

AC:

143455

AN:

152148

Hom.:

67701

Cov.:

AF XY:

0.942

AC XY:

70086

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.913

AC:

37874

AN:

41488

American (AMR)

AF:

0.932

AC:

14250

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.963

AC:

3342

AN:

3472

East Asian (EAS)

AF:

0.849

AC:

4366

AN:

5144

South Asian (SAS)

AF:

0.947

AC:

4563

AN:

4818

European-Finnish (FIN)

AF:

0.975

AC:

10343

AN:

10608

Middle Eastern (MID)

AF:

0.963

AC:

283

AN:

294

European-Non Finnish (NFE)

AF:

0.964

AC:

65545

AN:

68010

Other (OTH)

AF:

0.946

AC:

1995

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

406

812

1217

1623

2029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.957

Hom.:

29439

Bravo

AF:

0.938

Asia WGS

AF:

0.912

AC:

3173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.3

(source)

DANN

Benign

0.87

PhyloP100

0.23

PromoterAI

-0.085

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over