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. The variant received -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
• 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]

ENSG00000257878 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.0426 AC: 653 AN: 15338

American (AMR) AF: 0.138 AC: 3094 AN: 22348

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 3376 AN: 17392

East Asian (EAS) AF: 0.0181 AC: 608 AN: 33674

South Asian (SAS) AF: 0.131 AC: 7566 AN: 57748

European-Finnish (FIN) AF: 0.179 AC: 8742 AN: 48734

Middle Eastern (MID) AF: 0.157 AC: 626 AN: 3982

European-Non Finnish (NFE) AF: 0.256 AC: 100892 AN: 394368

Other (OTH) AF: 0.203 AC: 6361 AN: 31376

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

African (AFR) AF: 0.0488 AC: 2029 AN: 41550

American (AMR) AF: 0.150 AC: 2299 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3466

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5180

South Asian (SAS) AF: 0.124 AC: 601 AN: 4830

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10596

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17723 AN: 67994

Other (OTH) AF: 0.158 AC: 333 AN: 2114

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
PhyloP100		0.63
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: rs2540493; hg19: chr12-96415842;