rs2540493

Variant names:

• chr12-96022064-A-C
• rs2540493
• NM_000895.3:c.585+83T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-96022064-A-C
• chr12-96022064-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000895.3(LTA4H):​c.585+83T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 777,196 control chromosomes in the GnomAD database, including 18,725 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 0.17 (2879 hom., cov: 32)
  • Exomes 𝑓: 0.21 (15846 hom.)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.585+83T>G		intron_variant	Intron 5 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.585+83T>G		intron_variant	Intron 5 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25751 AN: 152118 Hom.: 2879 Cov.: 32

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.211 AC: 131918 AN: 624960 Hom.: 15846 AF XY: 0.208 AC XY: 68949 AN XY: 331032

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.0181

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.169 AC: 25748 AN: 152236 Hom.: 2879 Cov.: 32 AF XY: 0.163 AC XY: 12104 AN XY: 74430

Gnomad4 AFR AF: 0.0488

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.158

Alfa AF: 0.196 Hom.: 409

Bravo AF: 0.163

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.47

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: rs2540493; hg19: chr12-96415842;