chr12-96035599-G-A

Variant names:

• chr12-96035599-G-A
• rs17525495
• ENST00000552789.5:c.88-6414C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 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]

ENSG00000307169 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000552789.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	NM_001256643.1		c.88-6414C>T		intron	N/A	NP_001243572.1
	LTA4H	NM_001256644.1		c.88-6414C>T		intron	N/A	NP_001243573.1
	LTA4H	NM_000895.3	MANE Select	c.-80C>T		upstream_gene	N/A	NP_000886.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA4H	ENST00000552789.5	TSL:1	c.88-6414C>T		intron	N/A	ENSP00000449958.1
	LTA4H	ENST00000548852.5	TSL:2	n.-80C>T		non_coding_transcript_exon	Exon 1 of 18	ENSP00000449340.1
	ENSG00000307169	ENST00000824362.1		n.261G>A		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.0956 AC: 2879 AN: 30126

American (AMR) AF: 0.0835 AC: 2458 AN: 29426

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 1534 AN: 21190

East Asian (EAS) AF: 0.283 AC: 9779 AN: 34518

South Asian (SAS) AF: 0.206 AC: 14536 AN: 70678

European-Finnish (FIN) AF: 0.198 AC: 9429 AN: 47520

Middle Eastern (MID) AF: 0.0890 AC: 478 AN: 5368

European-Non Finnish (NFE) AF: 0.0723 AC: 75040 AN: 1038460

Other (OTH) AF: 0.101 AC: 5562 AN: 54828

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

African (AFR) AF: 0.0941 AC: 3909 AN: 41536

American (AMR) AF: 0.0839 AC: 1284 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1534 AN: 5146

South Asian (SAS) AF: 0.218 AC: 1051 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10576

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5132 AN: 68016

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0843 Hom.: 76

Bravo AF: 0.0908

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.93
PhyloP100		0.012
PromoterAI		-0.051	Neutral
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: rs17525495; hg19: chr12-96429377; COSMIC: COSV57382008; COSMIC: COSV57382008;