rs2540482

Variant names:

• chr12-96041102-C-T
• rs2540482
• ENST00000552789.5:c.87+2187G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552789.5(LTA4H):​c.87+2187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,030 control chromosomes in the GnomAD database, including 40,541 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 0.73 (40541 hom., cov: 33)
• Consequence: LTA4H ENST00000552789.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 13 publications found

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]

ENSG00000307169 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_001256643.1	c.87+2187G>A		intron_variant	Intron 1 of 18		NP_001243572.1
LTA4H	NM_001256644.1	c.87+2187G>A		intron_variant	Intron 1 of 17		NP_001243573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000552789.5	c.87+2187G>A		intron_variant	Intron 1 of 18	1		ENSP00000449958.1
LTA4H	ENST00000413268.6	c.87+2187G>A		intron_variant	Intron 1 of 17	2		ENSP00000395051.2
ENSG00000307169	ENST00000824362.1	n.271+5493C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110358 AN: 151912 Hom.: 40526 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.726 AC: 110413 AN: 152030 Hom.: 40541 Cov.: 33 AF XY: 0.724 AC XY: 53788 AN XY: 74328

African (AFR) AF: 0.725 AC: 30053 AN: 41438

American (AMR) AF: 0.578 AC: 8830 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2278 AN: 5158

South Asian (SAS) AF: 0.768 AC: 3704 AN: 4824

European-Finnish (FIN) AF: 0.819 AC: 8640 AN: 10548

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52001 AN: 68006

Other (OTH) AF: 0.699 AC: 1473 AN: 2106

Alfa AF: 0.758 Hom.: 21139

Bravo AF: 0.704

Asia WGS AF: 0.618 AC: 2148 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2540482; hg19: chr12-96434880;