rs17677715

chr12-96020673-T-C

Variant summary

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

The NM_000895.3(LTA4H):c.638+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 162,474 control chromosomes in the GnomAD database, including 1,762 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 0.13 (1595 hom., cov: 32)
  • Exomes 𝑓: 0.16 (167 hom.)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_000895.3	c.638+412A>G		intron_variant		ENST00000228740.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.638+412A>G		intron_variant		1	NM_000895.3	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19129 AN: 152172 Hom.: 1595 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.0817

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.160 AC: 1633 AN: 10184 Hom.: 167 Cov.: 0 AF XY: 0.153 AC XY: 786 AN XY: 5128

Gnomad4 AFR exome AF: 0.00909

Gnomad4 AMR exome AF: 0.0857

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.126 AC: 19130 AN: 152290 Hom.: 1595 Cov.: 32 AF XY: 0.122 AC XY: 9111 AN XY: 74460

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.120

Alfa AF: 0.149 Hom.: 223

Bravo AF: 0.121

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.0
Dann	Benign	0.52

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: rs17677715; hg19: chr12-96414451;