chr12-96035599-G-A

Position:

• chr12-96035599-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552789.5(LTA4H):​c.88-6414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,484,296 control chromosomes in the GnomAD database, including 8,502 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 0.10 (1047 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7455 hom.)
• Consequence: LTA4H ENST00000552789.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA4H	NM_000895.3			upstream_gene_variant		ENST00000228740.7	NP_000886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA4H	ENST00000552789.5	c.88-6414C>T		intron_variant		1		ENSP00000449958
LTA4H	ENST00000413268.6	c.88-6414C>T		intron_variant		2		ENSP00000395051
LTA4H	ENST00000548852.5	c.-80C>T		5_prime_UTR_variant, NMD_transcript_variant	1/18	2		ENSP00000449340
LTA4H	ENST00000228740.7			upstream_gene_variant		1	NM_000895.3	ENSP00000228740	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15592 AN: 152064 Hom.: 1041 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0956

GnomAD4 exome AF: 0.0914 AC: 121695 AN: 1332114 Hom.: 7455 Cov.: 31 AF XY: 0.0944 AC XY: 61280 AN XY: 649264

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.0835

Gnomad4 ASJ exome AF: 0.0724

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.0723

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.103 AC: 15615 AN: 152182 Hom.: 1047 Cov.: 32 AF XY: 0.111 AC XY: 8228 AN XY: 74368

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0837 Hom.: 73

Bravo AF: 0.0908

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.93

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: rs17525495; hg19: chr12-96429377; COSMIC: COSV57382008; COSMIC: COSV57382008;