10-45377416-C-T

Variant names:

• chr10-45377416-C-T
• rs3824612
• NM_000698.5:c.150+2987C>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.150+2987C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 150,986 control chromosomes in the GnomAD database, including 8,908 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 0.31 (8908 hom., cov: 28)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 16 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 = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000698.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	NM_000698.5	MANE Select	c.150+2987C>T		intron	N/A	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.150+2987C>T		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.150+2987C>T		intron	N/A	NP_001243082.1	P09917-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.150+2987C>T		intron	N/A	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.150+2987C>T		intron	N/A	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.150+2987C>T		intron	N/A	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46365 AN: 150866 Hom.: 8903 Cov.: 28

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.307 AC: 46363 AN: 150986 Hom.: 8908 Cov.: 28 AF XY: 0.317 AC XY: 23342 AN XY: 73678

African (AFR) AF: 0.0746 AC: 3075 AN: 41214

American (AMR) AF: 0.429 AC: 6485 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1030 AN: 3460

East Asian (EAS) AF: 0.512 AC: 2595 AN: 5068

South Asian (SAS) AF: 0.324 AC: 1542 AN: 4756

European-Finnish (FIN) AF: 0.473 AC: 4905 AN: 10368

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25511 AN: 67710

Other (OTH) AF: 0.327 AC: 685 AN: 2092

Alfa AF: 0.357 Hom.: 10482

Bravo AF: 0.297

Asia WGS AF: 0.367 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		-0.33
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: rs3824612; hg19: chr10-45872864;