12-96029046-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000895.3(LTA4H):c.290+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,558,418 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (105 hom.)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-96029046-C-G is Benign according to our data. Variant chr12-96029046-C-G is described in ClinVar as [Benign]. Clinvar id is 718095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_000895.3	c.290+9G>C		intron_variant		ENST00000228740.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.290+9G>C		intron_variant		1	NM_000895.3	P1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3295 AN: 152116 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00583 AC: 1258 AN: 215640 Hom.: 32 AF XY: 0.00404 AC XY: 474 AN XY: 117416

Gnomad AFR exome AF: 0.0754

Gnomad AMR exome AF: 0.00427

Gnomad ASJ exome AF: 0.000482

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000419

Gnomad FIN exome AF: 0.0000480

Gnomad NFE exome AF: 0.000156

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00222 AC: 3119 AN: 1406184 Hom.: 105 Cov.: 28 AF XY: 0.00187 AC XY: 1309 AN XY: 698412

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.000911

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000941

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.0217 AC: 3304 AN: 152234 Hom.: 123 Cov.: 32 AF XY: 0.0203 AC XY: 1514 AN XY: 74438

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00621 Hom.: 7

Bravo AF: 0.0251

Asia WGS AF: 0.00578 AC: 20 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.8
Dann	Benign	0.61

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: rs114493880; hg19: chr12-96422824;