dbSNP rs17677715: LTA4H:c.638+412A>G (chr12-96020673-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.638+412A>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 162,474 control chromosomes in the GnomAD database, including 1,762 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 ( 1595 hom., cov: 32)

Exomes 𝑓: 0.16 ( 167 hom. )

Consequence

LTA4H
NM_000895.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

13 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3 link	c.638+412A>G		intron_variant	Intron 6 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.638+412A>G		intron_variant	Intron 6 of 18	1	NM_000895.3	ENSP00000228740.2		P09960-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19129

AN:

152172

Hom.:

1595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0182

Gnomad SAS

AF:

0.0817

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.121

GnomAD4 exome

AF:

0.160

AC:

1633

AN:

10184

Hom.:

167

Cov.:

AF XY:

0.153

AC XY:

786

AN XY:

5128

show subpopulations

African (AFR)

AF:

0.00909

AC:

AN:

110

American (AMR)

AF:

0.0857

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

AN:

160

East Asian (EAS)

AF:

0.0161

AC:

AN:

124

South Asian (SAS)

AF:

0.0926

AC:

110

AN:

1188

European-Finnish (FIN)

AF:

0.153

AC:

AN:

628

Middle Eastern (MID)

AF:

0.135

AC:

AN:

668

European-Non Finnish (NFE)

AF:

0.182

AC:

1188

AN:

6526

Other (OTH)

AF:

0.173

AC:

123

AN:

710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

128

193

257

321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.126

AC:

19130

AN:

152290

Hom.:

1595

Cov.:

AF XY:

0.122

AC XY:

9111

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0362

AC:

1506

AN:

41574

American (AMR)

AF:

0.120

AC:

1837

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

432

AN:

3472

East Asian (EAS)

AF:

0.0183

AC:

AN:

5194

South Asian (SAS)

AF:

0.0824

AC:

398

AN:

4830

European-Finnish (FIN)

AF:

0.135

AC:

1431

AN:

10604

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

12992

AN:

67998

Other (OTH)

AF:

0.120

AC:

252

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

827

1654

2482

3309

4136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.149

Hom.:

223

Bravo

AF:

0.121

Asia WGS

AF:

0.0460

AC:

161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.0

(source)

DANN

Benign

0.52

PhyloP100

0.037

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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