rs2660880

Positions:

• chr12-96007474-G-A
• chr12-96007474-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_000895.3	c.1435-1065C>T		intron_variant		ENST00000228740.7
LOC102723340	XR_945236.4	n.741-2487G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.1435-1065C>T		intron_variant		1	NM_000895.3	P1
	ENST00000551849.2	n.342-2487G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0604 Hom.: 451

Bravo AF: 0.0413

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.47
DANN	Benign	0.61

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: rs2660880; hg19: chr12-96401252;