dbSNP rs10492226: LTA4H:c.1380-1063A>T (chr12-96010211-T-A) – 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.1380-1063A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,264 control chromosomes in the GnomAD database, including 500 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 0.054 ( 500 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

LTA4H
NM_000895.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387

Publications

5 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:

LOC102723340 (HGNC:):

LOC102723340 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000895.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTA4H	NM_000895.3	MANE Select	c.1380-1063A>T	intron	N/A	NP_000886.1	A0A140VK27
LTA4H	NM_001256643.1		c.1308-1063A>T	intron	N/A	NP_001243572.1	P09960-4
LTA4H	NM_001414263.1		c.1380-1063A>T	intron	N/A	NP_001401192.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTA4H	ENST00000228740.7	TSL:1 MANE Select	c.1380-1063A>T	intron	N/A	ENSP00000228740.2	P09960-1
LTA4H	ENST00000552789.5	TSL:1	c.1308-1063A>T	intron	N/A	ENSP00000449958.1	P09960-4
LTA4H	ENST00000537111.6	TSL:1	n.1048A>T	non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8180

AN:

152146

Hom.:

500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0445

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0538

AC:

8197

AN:

152264

Hom.:

500

Cov.:

AF XY:

0.0527

AC XY:

3923

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.147

AC:

6110

AN:

41520

American (AMR)

AF:

0.0234

AC:

358

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0568

AC:

197

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0692

AC:

334

AN:

4828

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1062

AN:

68022

Other (OTH)

AF:

0.0445

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

363

726

1090

1453

1816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0385

Hom.:

Bravo

AF:

0.0593

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

(source)

DANN

Benign

0.58

PhyloP100

-0.39

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over