ENST00000552789.5:c.87+6647A>C

Variant names:

• chr12-96036642-T-G
• rs2660899
• ENST00000552789.5:c.87+6647A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LTA4H	NM_001256643.1	c.87+6647A>C		intron_variant	Intron 1 of 18		NP_001243572.1
LTA4H	NM_001256644.1	c.87+6647A>C		intron_variant	Intron 1 of 17		NP_001243573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000552789.5	c.87+6647A>C		intron_variant	Intron 1 of 18	1		ENSP00000449958.1
LTA4H	ENST00000413268.6	c.87+6647A>C		intron_variant	Intron 1 of 17	2		ENSP00000395051.2
ENSG00000307169	ENST00000824362.1	n.271+1033T>G		intron_variant	Intron 1 of 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

African (AFR) AF: 0.882 AC: 36605 AN: 41504

American (AMR) AF: 0.644 AC: 9843 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2523 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2819 AN: 5162

South Asian (SAS) AF: 0.745 AC: 3588 AN: 4814

European-Finnish (FIN) AF: 0.928 AC: 9827 AN: 10584

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56493 AN: 67990

Other (OTH) AF: 0.776 AC: 1641 AN: 2114

Alfa AF: 0.809 Hom.: 84465

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
PhyloP100		-2.1
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: rs2660899; hg19: chr12-96430420;