10-45426429-C-T

Variant names:

• chr10-45426429-C-T
• rs3780905
• NM_000698.5:c.834+1297C>T

Variant summary

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

The NM_000698.5(ALOX5):​c.834+1297C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,308 control chromosomes in the GnomAD database, including 845 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 0.053 (845 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.834+1297C>T		intron_variant	Intron 6 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.834+1297C>T		intron_variant	Intron 6 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.834+1297C>T		intron_variant	Intron 6 of 12	1		ENSP00000437634.1
ALOX5	ENST00000483623.2	n.237+1297C>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8059 AN: 152190 Hom.: 846 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0529 AC: 8054 AN: 152308 Hom.: 845 Cov.: 33 AF XY: 0.0573 AC XY: 4269 AN XY: 74468

African (AFR) AF: 0.0103 AC: 429 AN: 41584

American (AMR) AF: 0.0457 AC: 699 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2665 AN: 5170

South Asian (SAS) AF: 0.119 AC: 572 AN: 4826

European-Finnish (FIN) AF: 0.0589 AC: 625 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2676 AN: 68028

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0370 Hom.: 103

Bravo AF: 0.0536

Asia WGS AF: 0.255 AC: 886 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	2.3
DANN	Benign	0.50
PhyloP100		-0.38
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: rs3780905; hg19: chr10-45921877;