12-96036005-C-T

Position:

• chr12-96036005-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000552789.5(LTA4H):​c.88-6820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,092 control chromosomes in the GnomAD database, including 4,620 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 0.24 (4620 hom., cov: 32)
• Consequence: LTA4H ENST00000552789.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.97

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_001256643.1	c.88-6820G>A		intron_variant
LTA4H	NM_001256644.1	c.88-6820G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000552789.5	c.88-6820G>A		intron_variant		1
LTA4H	ENST00000413268.6	c.88-6820G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35780 AN: 151974 Hom.: 4621 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.235 AC: 35780 AN: 152092 Hom.: 4620 Cov.: 32 AF XY: 0.230 AC XY: 17066 AN XY: 74332

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.220

Alfa AF: 0.268 Hom.: 5667

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.0010
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2540487; hg19: chr12-96429783;