chr10-45401707-A-T

Position:

• chr10-45401707-A-T

Variant summary

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

The NM_000698.5(ALOX5):​c.431+5771A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,186 control chromosomes in the GnomAD database, including 52,553 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 0.83 (52553 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

Genes affected

ALOX5 (HGNC:435): (arachidonate 5-lipoxygenase) This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.431+5771A>T		intron_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.431+5771A>T		intron_variant		1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.431+5771A>T		intron_variant		1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126071 AN: 152068 Hom.: 52503 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.829 AC: 126178 AN: 152186 Hom.: 52553 Cov.: 32 AF XY: 0.829 AC XY: 61678 AN XY: 74394

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.815

Alfa AF: 0.830 Hom.: 6550

Bravo AF: 0.835

Asia WGS AF: 0.779 AC: 2708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.75

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: rs7099684; hg19: chr10-45897155;