chr10-45375113-T-G

Variant names:

• chr10-45375113-T-G
• rs1864414
• NM_000698.5:c.150+684T>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.150+684T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,934 control chromosomes in the GnomAD database, including 2,215 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 0.17 (2215 hom., cov: 32)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.150+684T>G		intron_variant	Intron 1 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.150+684T>G		intron_variant	Intron 1 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.150+684T>G		intron_variant	Intron 1 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25497 AN: 151816 Hom.: 2208 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.168 AC: 25535 AN: 151934 Hom.: 2215 Cov.: 32 AF XY: 0.169 AC XY: 12571 AN XY: 74216

African (AFR) AF: 0.177 AC: 7330 AN: 41434

American (AMR) AF: 0.134 AC: 2050 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.183 AC: 941 AN: 5134

South Asian (SAS) AF: 0.190 AC: 911 AN: 4798

European-Finnish (FIN) AF: 0.194 AC: 2051 AN: 10558

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11075 AN: 67962

Other (OTH) AF: 0.167 AC: 353 AN: 2110

Alfa AF: 0.163 Hom.: 1424

Bravo AF: 0.163

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.87
PhyloP100		0.72
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: rs1864414; hg19: chr10-45870561;