chr10-45416789-T-C

Variant names:

• chr10-45416789-T-C
• rs11239523
• NM_000698.5:c.554+4476T>C

Variant summary

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

The NM_000698.5(ALOX5):​c.554+4476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,728 control chromosomes in the GnomAD database, including 1,593 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 0.14 (1593 hom., cov: 31)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.554+4476T>C		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.554+4476T>C		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.554+4476T>C		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20608 AN: 151610 Hom.: 1590 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.136 AC: 20627 AN: 151728 Hom.: 1593 Cov.: 31 AF XY: 0.139 AC XY: 10276 AN XY: 74160

African (AFR) AF: 0.112 AC: 4642 AN: 41330

American (AMR) AF: 0.0979 AC: 1493 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.0844 AC: 405 AN: 4796

European-Finnish (FIN) AF: 0.226 AC: 2384 AN: 10536

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10794 AN: 67872

Other (OTH) AF: 0.123 AC: 259 AN: 2108

Alfa AF: 0.143 Hom.: 874

Bravo AF: 0.122

Asia WGS AF: 0.0410 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.53
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: rs11239523; hg19: chr10-45912237;