Variant chr12-96006401-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000895.3(LTA4H):c.1443A>T(p.Glu481Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,599,542 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 122 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 111 hom. )

Consequence

LTA4H
NM_000895.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.602

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018874407).

BP6

Variant 12-96006401-T-A is Benign according to our data. Variant chr12-96006401-T-A is described in ClinVar as [Benign]. Clinvar id is 718094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA4H	NM_000895.3 link	c.1443A>T	p.Glu481Asp	missense_variant	16/19	ENST00000228740.7	NP_000886.1	P09960-1A0A140VK27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7 link	c.1443A>T	p.Glu481Asp	missense_variant	16/19	1	NM_000895.3	ENSP00000228740.2		P09960-1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3353

AN:

152186

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00969

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00586

AC:

1459

AN:

248866

Hom.:

AF XY:

0.00415

AC XY:

558

AN XY:

134530

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.000599

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00237

AC:

3424

AN:

1447238

Hom.:

111

Cov.:

AF XY:

0.00199

AC XY:

1431

AN XY:

720524

show subpopulations

Gnomad4 AFR exome

AF:

0.0778

Gnomad4 AMR exome

AF:

0.00560

Gnomad4 ASJ exome

AF:

0.000848

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00567

GnomAD4 genome

AF:

0.0221

AC:

3364

AN:

152304

Hom.:

122

Cov.:

AF XY:

0.0206

AC XY:

1535

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0760

Gnomad4 AMR

AF:

0.00967

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.0255

ESP6500AA

AF:

0.0742

AC:

327

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00705

AC:

856

Asia WGS

AF:

0.00664

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

L;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.097

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.20

MutPred

0.38

Gain of catalytic residue at N485 (P = 0.0428);.;.;

MVP

0.40

MPC

0.24

ClinPred

0.0034

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over