dbSNP rs17525495: LTA4H:c.88-6414C>T (chr12-96035599-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000552789.5(LTA4H):c.88-6414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,484,296 control chromosomes in the GnomAD database, including 8,502 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 0.10 ( 1047 hom., cov: 32)

Exomes 𝑓: 0.091 ( 7455 hom. )

Consequence

LTA4H
ENST00000552789.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Publications

44 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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.-80C>T		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.-80C>T		upstream_gene_variant		1	NM_000895.3	ENSP00000228740.2		P09960-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15592

AN:

152064

Hom.:

1041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0838

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.0956

GnomAD4 exome

AF:

0.0914

AC:

121695

AN:

1332114

Hom.:

7455

Cov.:

AF XY:

0.0944

AC XY:

61280

AN XY:

649264

show subpopulations

African (AFR)

AF:

0.0956

AC:

2879

AN:

30126

American (AMR)

AF:

0.0835

AC:

2458

AN:

29426

Ashkenazi Jewish (ASJ)

AF:

0.0724

AC:

1534

AN:

21190

East Asian (EAS)

AF:

0.283

AC:

9779

AN:

34518

South Asian (SAS)

AF:

0.206

AC:

14536

AN:

70678

European-Finnish (FIN)

AF:

0.198

AC:

9429

AN:

47520

Middle Eastern (MID)

AF:

0.0890

AC:

478

AN:

5368

European-Non Finnish (NFE)

AF:

0.0723

AC:

75040

AN:

1038460

Other (OTH)

AF:

0.101

AC:

5562

AN:

54828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5153

10306

15458

20611

25764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3102

6204

9306

12408

15510

<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:

15615

AN:

152182

Hom.:

1047

Cov.:

AF XY:

0.111

AC XY:

8228

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0941

AC:

3909

AN:

41536

American (AMR)

AF:

0.0839

AC:

1284

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3472

East Asian (EAS)

AF:

0.298

AC:

1534

AN:

5146

South Asian (SAS)

AF:

0.218

AC:

1051

AN:

4818

European-Finnish (FIN)

AF:

0.203

AC:

2146

AN:

10576

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0755

AC:

5132

AN:

68016

Other (OTH)

AF:

0.104

AC:

220

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

690

1381

2071

2762

3452

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:

0.0843

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

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.9

(source)

DANN

Benign

0.93

PhyloP100

0.012

PromoterAI

-0.051

Neutral

(source)

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