12-96032219-T-G

Variant names:

• chr12-96032219-T-G
• rs2660898
• NM_000895.3:c.160-3034A>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.160-3034A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,156 control chromosomes in the GnomAD database, including 7,244 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 0.30 (7244 hom., cov: 33)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 19 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]

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 (EAS) allele frequency at 95% confidence interval = 0.401 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.160-3034A>C		intron	N/A	NP_000886.1	A0A140VK27
	LTA4H	NM_001256643.1		c.88-3034A>C		intron	N/A	NP_001243572.1	P09960-4
	LTA4H	NM_001414263.1		c.160-3034A>C		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.160-3034A>C		intron	N/A	ENSP00000228740.2	P09960-1
	LTA4H	ENST00000552789.5	TSL:1	c.88-3034A>C		intron	N/A	ENSP00000449958.1	P09960-4
	LTA4H	ENST00000852107.1		c.160-3034A>C		intron	N/A	ENSP00000522166.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45959 AN: 152038 Hom.: 7234 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.302 AC: 45990 AN: 152156 Hom.: 7244 Cov.: 33 AF XY: 0.303 AC XY: 22569 AN XY: 74382

African (AFR) AF: 0.223 AC: 9257 AN: 41524

American (AMR) AF: 0.254 AC: 3886 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2155 AN: 5182

South Asian (SAS) AF: 0.356 AC: 1720 AN: 4832

European-Finnish (FIN) AF: 0.372 AC: 3931 AN: 10558

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23103 AN: 67986

Other (OTH) AF: 0.283 AC: 599 AN: 2114

Alfa AF: 0.303 Hom.: 868

Bravo AF: 0.288

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.52
PhyloP100		-0.48
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: rs2660898; hg19: chr12-96425997;