12-96030004-T-C

Variant names:

• chr12-96030004-T-C
• rs2660896
• NM_000895.3:c.160-819A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000895.3(LTA4H):​c.160-819A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,838 control chromosomes in the GnomAD database, including 20,975 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 0.50 (20975 hom., cov: 30)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.160-819A>G		intron_variant	Intron 1 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.160-819A>G		intron_variant	Intron 1 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76075 AN: 151720 Hom.: 20930 Cov.: 30

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.502 AC: 76176 AN: 151838 Hom.: 20975 Cov.: 30 AF XY: 0.496 AC XY: 36843 AN XY: 74208

African (AFR) AF: 0.748 AC: 30974 AN: 41382

American (AMR) AF: 0.360 AC: 5497 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2620 AN: 5160

South Asian (SAS) AF: 0.473 AC: 2275 AN: 4812

European-Finnish (FIN) AF: 0.391 AC: 4119 AN: 10544

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27841 AN: 67894

Other (OTH) AF: 0.454 AC: 958 AN: 2112

Alfa AF: 0.427 Hom.: 8584

Bravo AF: 0.509

Asia WGS AF: 0.487 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2660896; hg19: chr12-96423782;