12-96036005-C-T

Variant names:

• chr12-96036005-C-T
• rs2540487
• ENST00000552789.5:c.88-6820G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001256643.1(LTA4H):​c.88-6820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,092 control chromosomes in the GnomAD database, including 4,620 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 0.24 (4620 hom., cov: 32)
• Consequence: LTA4H NM_001256643.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.97
• Publications: 14 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]

ENSG00000307169 (HGNC:):

TRD-GTC2-8 (HGNC:34802):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256643.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	NM_001256643.1		c.88-6820G>A		intron	N/A	NP_001243572.1
	LTA4H	NM_001256644.1		c.88-6820G>A		intron	N/A	NP_001243573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	ENST00000552789.5	TSL:1	c.88-6820G>A		intron	N/A	ENSP00000449958.1
	LTA4H	ENST00000413268.6	TSL:2	c.88-6820G>A		intron	N/A	ENSP00000395051.2
	ENSG00000307169	ENST00000824362.1		n.271+396C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35780 AN: 151974 Hom.: 4621 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.235 AC: 35780 AN: 152092 Hom.: 4620 Cov.: 32 AF XY: 0.230 AC XY: 17066 AN XY: 74332

African (AFR) AF: 0.148 AC: 6154 AN: 41492

American (AMR) AF: 0.196 AC: 3001 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3470

East Asian (EAS) AF: 0.188 AC: 977 AN: 5184

South Asian (SAS) AF: 0.169 AC: 812 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2431 AN: 10568

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20759 AN: 67958

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.264 Hom.: 7217

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.0010
DANN	Benign	0.77
PhyloP100		-9.0
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2540487; hg19: chr12-96429783;