12-96014985-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_000895.3(LTA4H):c.1074G>A(p.Gly358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,609,934 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (14 hom.)
• Consequence: LTA4H NM_000895.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 12-96014985-C-T is Benign according to our data. Variant chr12-96014985-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 786932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTA4H	NM_000895.3	c.1074G>A	p.Gly358=	synonymous_variant	12/19	ENST00000228740.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.1074G>A	p.Gly358=	synonymous_variant	12/19	1	NM_000895.3	P1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00186 AC: 457 AN: 246326 Hom.: 4 AF XY: 0.00211 AC XY: 281 AN XY: 132896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00972

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00297

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00149 AC: 2166 AN: 1457724 Hom.: 14 Cov.: 31 AF XY: 0.00160 AC XY: 1161 AN XY: 724888

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.00194

Gnomad4 ASJ exome AF: 0.00977

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00296

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00145 AC: 220 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74420

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00151

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00344

EpiControl AF: 0.00291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	LTA4H: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	8.8
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147001898; hg19: chr12-96408763;