12-96036642-T-G

Position:

• chr12-96036642-T-G

Variant summary

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

The ENST00000552789.5(LTA4H):​c.87+6647A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,128 control chromosomes in the GnomAD database, including 51,437 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 0.82 (51437 hom., cov: 31)
• Consequence: LTA4H ENST00000552789.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_001256643.1	c.87+6647A>C		intron_variant
LTA4H	NM_001256644.1	c.87+6647A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000552789.5	c.87+6647A>C		intron_variant		1
LTA4H	ENST00000413268.6	c.87+6647A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124168 AN: 152010 Hom.: 51408 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.817 AC: 124246 AN: 152128 Hom.: 51437 Cov.: 31 AF XY: 0.814 AC XY: 60553 AN XY: 74366

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.776

Alfa AF: 0.810 Hom.: 66893

Bravo AF: 0.796

Asia WGS AF: 0.667 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2660899; hg19: chr12-96430420;