chr10-45440296-C-T

Position:

• chr10-45440296-C-T

Variant summary

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

The NM_000698.5(ALOX5):​c.982-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 940,476 control chromosomes in the GnomAD database, including 124,153 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 0.51 (19877 hom., cov: 32)
  • Exomes 𝑓: 0.51 (104276 hom.)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.982-134C>T		intron_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.982-134C>T		intron_variant		1	NM_000698.5	ENSP00000363512	P1
ALOX5	ENST00000542434.5	c.982-134C>T		intron_variant		1		ENSP00000437634

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77172 AN: 151846 Hom.: 19850 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.511 AC: 402961 AN: 788512 Hom.: 104276 AF XY: 0.506 AC XY: 203731 AN XY: 402344

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.509

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.508 AC: 77248 AN: 151964 Hom.: 19877 Cov.: 32 AF XY: 0.506 AC XY: 37572 AN XY: 74276

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.514

Alfa AF: 0.480 Hom.: 7631

Bravo AF: 0.519

Asia WGS AF: 0.509 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3780914; hg19: chr10-45935744;