dbSNP rs17525488: LTA4H:c.88-6475delA (chr12-96035659-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000552789.5(LTA4H):c.88-6475delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,430,700 control chromosomes in the GnomAD database, including 8,003 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1048 hom., cov: 31)

Exomes 𝑓: 0.090 ( 6955 hom. )

Consequence

LTA4H
ENST00000552789.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.569

Publications

9 publications found

Variant links:

Genes affected

LTA4H (HGNC:6710): (leukotriene A4 hydrolase) The protein encoded by this gene is an enzyme that contains both hydrolase and aminopeptidase activities. The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. The aminopeptidase activity has been shown to degrade proline-glycine-proline (PGP), a neutrophil chemoattractant and biomarker for chronic obstructive pulmonary disease (COPD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LTA4H links:

ENSG00000307169 (HGNC:):

ENSG00000307169 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3 link	c.-141delA		upstream_gene_variant		ENST00000228740.7	NP_000886.1	P09960-1A0A140VK27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7 link	c.-141delA		upstream_gene_variant		1	NM_000895.3	ENSP00000228740.2		P09960-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15569

AN:

151894

Hom.:

1042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0839

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.0955

GnomAD4 exome

AF:

0.0900

AC:

115143

AN:

1278688

Hom.:

6955

Cov.:

AF XY:

0.0927

AC XY:

57307

AN XY:

617976

show subpopulations

African (AFR)

AF:

0.0941

AC:

2627

AN:

27910

American (AMR)

AF:

0.0762

AC:

1539

AN:

20196

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

1312

AN:

18434

East Asian (EAS)

AF:

0.281

AC:

9412

AN:

33446

South Asian (SAS)

AF:

0.206

AC:

12592

AN:

61008

European-Finnish (FIN)

AF:

0.197

AC:

8633

AN:

43798

Middle Eastern (MID)

AF:

0.0893

AC:

385

AN:

4312

European-Non Finnish (NFE)

AF:

0.0721

AC:

73345

AN:

1017014

Other (OTH)

AF:

0.101

AC:

5298

AN:

52570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4465

8929

13394

17858

22323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3070

6140

9210

12280

15350

<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:

0.103

AC:

15592

AN:

152012

Hom.:

1048

Cov.:

AF XY:

0.111

AC XY:

8215

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0941

AC:

3905

AN:

41490

American (AMR)

AF:

0.0840

AC:

1284

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3472

East Asian (EAS)

AF:

0.299

AC:

1531

AN:

5124

South Asian (SAS)

AF:

0.219

AC:

1053

AN:

4812

European-Finnish (FIN)

AF:

0.202

AC:

2130

AN:

10526

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0755

AC:

5131

AN:

67994

Other (OTH)

AF:

0.104

AC:

219

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

677

1354

2030

2707

3384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0838

Hom.:

Bravo

AF:

0.0908

Asia WGS

AF:

0.260

AC:

902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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