NM_000698.5:c.554+5010T>G

Variant names:

• chr10-45417323-T-G
• rs11239524
• NM_000698.5:c.554+5010T>G

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+5010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,194 control chromosomes in the GnomAD database, including 1,683 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 (1683 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.554+5010T>G		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+5010T>G		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.554+5010T>G		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21638 AN: 152076 Hom.: 1678 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.142 AC: 21667 AN: 152194 Hom.: 1683 Cov.: 32 AF XY: 0.143 AC XY: 10655 AN XY: 74408

African (AFR) AF: 0.148 AC: 6145 AN: 41528

American (AMR) AF: 0.103 AC: 1577 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3472

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

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1960 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10642 AN: 67990

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.148 Hom.: 4989

Bravo AF: 0.134

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.51
PhyloP100		-1.2
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: rs11239524; hg19: chr10-45912771;