rs1978331

Variant names:

• chr12-96015423-A-G
• rs1978331
• NM_000895.3:c.1059+160T>C

Variant summary

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

The NM_000895.3(LTA4H):​c.1059+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,034 control chromosomes in the GnomAD database, including 20,283 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 0.49 (20283 hom., cov: 32)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 35 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.1059+160T>C		intron_variant	Intron 11 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.1059+160T>C		intron_variant	Intron 11 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74926 AN: 151916 Hom.: 20246 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.493 AC: 75019 AN: 152034 Hom.: 20283 Cov.: 32 AF XY: 0.487 AC XY: 36212 AN XY: 74294

African (AFR) AF: 0.733 AC: 30419 AN: 41478

American (AMR) AF: 0.351 AC: 5368 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2101 AN: 5154

South Asian (SAS) AF: 0.463 AC: 2236 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4115 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27985 AN: 67962

Other (OTH) AF: 0.446 AC: 942 AN: 2112

Alfa AF: 0.428 Hom.: 61704

Bravo AF: 0.500

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1978331; hg19: chr12-96409201;