rs6538697

chr12-96009832-T-Cchr12-96009832-T-G

Variant summary

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

The NM_000895.3(LTA4H):c.1380-684A>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 152,234 control chromosomes in the GnomAD database, including 1,551 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 (1551 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_000895.3	c.1380-684A>G		intron_variant		ENST00000228740.7
LOC102723340	XR_945236.4	n.741-129T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.1380-684A>G		intron_variant		1	NM_000895.3	P1
	ENST00000551849.2	n.342-129T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19439 AN: 152094 Hom.: 1543 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.128 AC: 19473 AN: 152212 Hom.: 1551 Cov.: 32 AF XY: 0.134 AC XY: 10006 AN XY: 74422

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0833 Hom.: 1367

Bravo AF: 0.119

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.4
Dann	Benign	0.71

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: rs6538697; hg19: chr12-96403610;