10-45384608-C-T

Variant names:

• chr10-45384608-C-T
• rs4948671
• NM_000698.5:c.349+1927C>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.349+1927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,892 control chromosomes in the GnomAD database, including 36,987 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 0.69 (36987 hom., cov: 30)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 9 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.349+1927C>T		intron_variant	Intron 2 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.349+1927C>T		intron_variant	Intron 2 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.349+1927C>T		intron_variant	Intron 2 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105047 AN: 151774 Hom.: 36936 Cov.: 30

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.692 AC: 105155 AN: 151892 Hom.: 36987 Cov.: 30 AF XY: 0.699 AC XY: 51912 AN XY: 74214

African (AFR) AF: 0.806 AC: 33365 AN: 41416

American (AMR) AF: 0.700 AC: 10692 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4418 AN: 5154

South Asian (SAS) AF: 0.592 AC: 2851 AN: 4816

European-Finnish (FIN) AF: 0.753 AC: 7935 AN: 10542

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41709 AN: 67920

Other (OTH) AF: 0.674 AC: 1421 AN: 2108

Alfa AF: 0.637 Hom.: 29814

Bravo AF: 0.697

Asia WGS AF: 0.725 AC: 2522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.62
PhyloP100		-0.40
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: rs4948671; hg19: chr10-45880056;