12-96024731-T-C

Variant names:

• chr12-96024731-T-C
• rs2540491
• NM_000895.3:c.412-184A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000895.3(LTA4H):​c.412-184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 150,668 control chromosomes in the GnomAD database, including 19,672 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 0.49 (19672 hom., cov: 27)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.412-184A>G		intron_variant	Intron 3 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.412-184A>G		intron_variant	Intron 3 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73473 AN: 150554 Hom.: 19636 Cov.: 27

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 73561 AN: 150668 Hom.: 19672 Cov.: 27 AF XY: 0.482 AC XY: 35461 AN XY: 73520

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.442

Alfa AF: 0.428 Hom.: 1835

Bravo AF: 0.495

Asia WGS AF: 0.448 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs2540491; hg19: chr12-96418509;