chr12-96028599-T-C

Variant names:

• chr12-96028599-T-C
• rs2247570
• NM_000895.3:c.290+456A>G

Variant summary

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

The NM_000895.3(LTA4H):​c.290+456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,146 control chromosomes in the GnomAD database, including 9,102 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 0.33 (9102 hom., cov: 32)
• Consequence: LTA4H NM_000895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 21 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 (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA4H	NM_000895.3	c.290+456A>G		intron_variant	Intron 2 of 18	ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000228740.7	c.290+456A>G		intron_variant	Intron 2 of 18	1	NM_000895.3	ENSP00000228740.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49774 AN: 152028 Hom.: 9096 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.327 AC: 49805 AN: 152146 Hom.: 9102 Cov.: 32 AF XY: 0.314 AC XY: 23385 AN XY: 74382

African (AFR) AF: 0.471 AC: 19554 AN: 41496

American (AMR) AF: 0.241 AC: 3690 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3466

East Asian (EAS) AF: 0.110 AC: 569 AN: 5178

South Asian (SAS) AF: 0.167 AC: 805 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1926 AN: 10600

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21388 AN: 67988

Other (OTH) AF: 0.293 AC: 619 AN: 2110

Alfa AF: 0.309 Hom.: 12568

Bravo AF: 0.340

Asia WGS AF: 0.139 AC: 485 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	2.2
DANN	Benign	0.71
PhyloP100		-0.37
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: rs2247570; hg19: chr12-96422377;