rs10751383

chr10-45442544-A-Cchr10-45442544-A-Gchr10-45442544-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000698.5(ALOX5):c.1273-494A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 154,744 control chromosomes in the GnomAD database, including 25,247 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 0.57 (24841 hom., cov: 34)
  • Exomes 𝑓: 0.55 (406 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.1273-494A>C		intron_variant		ENST00000374391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.1273-494A>C		intron_variant		1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.1273-494A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86355 AN: 152002 Hom.: 24806 Cov.: 34

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.549 AC: 1440 AN: 2624 Hom.: 406 AF XY: 0.558 AC XY: 742 AN XY: 1330

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.724

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.568 AC: 86444 AN: 152120 Hom.: 24841 Cov.: 34 AF XY: 0.565 AC XY: 42004 AN XY: 74366

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.563

Alfa AF: 0.560 Hom.: 15585

Bravo AF: 0.581

Asia WGS AF: 0.555 AC: 1931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.1
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs10751383; hg19: chr10-45937992; COSMIC: COSV65551248; COSMIC: COSV65551248;