dbSNP rs6538697: LTA4H:c.1380-684A>G (chr12-96009832-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000895.3(LTA4H):c.1380-684A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,234 control chromosomes in the GnomAD database, including 1,551 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 0.13 ( 1551 hom., cov: 32)

Exomes 𝑓: 0.045 ( 0 hom. )

Consequence

LTA4H
NM_000895.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

36 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:

ENSG00000257878 (HGNC:):

ENSG00000257878 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3 link	c.1380-684A>G		intron_variant	Intron 14 of 18	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.1380-684A>G		intron_variant	Intron 14 of 18	1	NM_000895.3	ENSP00000228740.2		P09960-1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19439

AN:

152094

Hom.:

1543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0941

Gnomad ASJ

AF:

0.0790

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0793

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.0455

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0714

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.128

AC:

19473

AN:

152212

Hom.:

1551

Cov.:

AF XY:

0.134

AC XY:

10006

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.174

AC:

7234

AN:

41514

American (AMR)

AF:

0.0942

AC:

1442

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0790

AC:

274

AN:

3470

East Asian (EAS)

AF:

0.294

AC:

1521

AN:

5168

South Asian (SAS)

AF:

0.224

AC:

1083

AN:

4834

European-Finnish (FIN)

AF:

0.207

AC:

2191

AN:

10582

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0793

AC:

5393

AN:

68018

Other (OTH)

AF:

0.122

AC:

257

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

841

1683

2524

3366

4207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0896

Hom.:

3217

Bravo

AF:

0.119

Asia WGS

AF:

0.266

AC:

922

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

(source)

DANN

Benign

0.71

PhyloP100

-0.028

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over