12-96010211-T-A

Variant names:

• chr12-96010211-T-A
• rs10492226
• ENST00000537111.6:n.1048A>T

Variant summary

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

The ENST00000537111.6(LTA4H):​n.1048A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,264 control chromosomes in the GnomAD database, including 500 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 0.054 (500 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LTA4H ENST00000537111.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 5 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]

LOC102723340 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.1380-1063A>T		intron_variant	Intron 14 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.1380-1063A>T		intron_variant	Intron 14 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8180 AN: 152146 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0445

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0538 AC: 8197 AN: 152264 Hom.: 500 Cov.: 32 AF XY: 0.0527 AC XY: 3923 AN XY: 74464

African (AFR) AF: 0.147 AC: 6110 AN: 41520

American (AMR) AF: 0.0234 AC: 358 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4828

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1062 AN: 68022

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0385 Hom.: 40

Bravo AF: 0.0593

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		-0.39
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: rs10492226; hg19: chr12-96403989;