rs2660880

Variant names:

• chr12-96007474-G-A
• rs2660880
• NM_000895.3:c.1435-1065C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-96007474-G-A
• chr12-96007474-G-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.1435-1065C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,304 control chromosomes in the GnomAD database, including 181 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 0.043 (181 hom., cov: 32)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000895.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	NM_000895.3	MANE Select	c.1435-1065C>T		intron	N/A	NP_000886.1	A0A140VK27
	LTA4H	NM_001256643.1		c.1363-1065C>T		intron	N/A	NP_001243572.1	P09960-4
	LTA4H	NM_001414263.1		c.1434+1620C>T		intron	N/A	NP_001401192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	ENST00000228740.7	TSL:1 MANE Select	c.1435-1065C>T		intron	N/A	ENSP00000228740.2	P09960-1
	LTA4H	ENST00000552789.5	TSL:1	c.1363-1065C>T		intron	N/A	ENSP00000449958.1	P09960-4
	LTA4H	ENST00000537111.6	TSL:1	n.1321-1065C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6490 AN: 152186 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0426 AC: 6486 AN: 152304 Hom.: 181 Cov.: 32 AF XY: 0.0391 AC XY: 2910 AN XY: 74478

African (AFR) AF: 0.0125 AC: 518 AN: 41560

American (AMR) AF: 0.0301 AC: 460 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4830

European-Finnish (FIN) AF: 0.0302 AC: 321 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4694 AN: 68026

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0588 Hom.: 551

Bravo AF: 0.0413

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs2660880; hg19: chr12-96401252;