12-96035659-CT-C

Position:

• chr12-96035659-CT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001256643.1(LTA4H):​c.88-6475delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,430,700 control chromosomes in the GnomAD database, including 8,003 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1048 hom., cov: 31)
  • Exomes 𝑓: 0.090 (6955 hom.)
• Consequence: LTA4H NM_001256643.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA4H	NM_001256643.1	c.88-6475delA		intron_variant			NP_001243572.1
LTA4H	NM_001256644.1	c.88-6475delA		intron_variant			NP_001243573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000552789.5	c.88-6475delA		intron_variant		1		ENSP00000449958.1
LTA4H	ENST00000413268.6	c.88-6475delA		intron_variant		2		ENSP00000395051.2
LTA4H	ENST00000548852.5	n.-141delA		upstream_gene_variant		2		ENSP00000449340.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15569 AN: 151894 Hom.: 1042 Cov.: 31

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0955

GnomAD4 exome AF: 0.0900 AC: 115143 AN: 1278688 Hom.: 6955 Cov.: 29 AF XY: 0.0927 AC XY: 57307 AN XY: 617976

Gnomad4 AFR exome AF: 0.0941

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.0721

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.103 AC: 15592 AN: 152012 Hom.: 1048 Cov.: 31 AF XY: 0.111 AC XY: 8215 AN XY: 74268

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0838 Hom.: 71

Bravo AF: 0.0908

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs17525488; hg19: chr12-96429437;