NM_000698.5:c.982-134C>T

Variant names:

• chr10-45440296-C-T
• rs3780914
• NM_000698.5:c.982-134C>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.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
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	NM_000698.5	MANE Select	c.982-134C>T		intron	N/A	NP_000689.1
	ALOX5	NM_001320861.2		c.982-134C>T		intron	N/A	NP_001307790.1
	ALOX5	NM_001256153.3		c.982-134C>T		intron	N/A	NP_001243082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.982-134C>T		intron	N/A	ENSP00000363512.2
	ALOX5	ENST00000542434.5	TSL:1	c.982-134C>T		intron	N/A	ENSP00000437634.1
	ALOX5	ENST00000475300.1	TSL:2	n.-134C>T		upstream_gene	N/A

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

African (AFR) AF: 0.464 AC: 8746 AN: 18850

American (AMR) AF: 0.664 AC: 17002 AN: 25602

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 8637 AN: 16652

East Asian (EAS) AF: 0.614 AC: 20722 AN: 33766

South Asian (SAS) AF: 0.418 AC: 23363 AN: 55910

European-Finnish (FIN) AF: 0.491 AC: 20755 AN: 42292

Middle Eastern (MID) AF: 0.534 AC: 2022 AN: 3784

European-Non Finnish (NFE) AF: 0.509 AC: 282298 AN: 554238

Other (OTH) AF: 0.519 AC: 19416 AN: 37418

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

African (AFR) AF: 0.477 AC: 19772 AN: 41430

American (AMR) AF: 0.600 AC: 9171 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3265 AN: 5168

South Asian (SAS) AF: 0.417 AC: 2008 AN: 4820

European-Finnish (FIN) AF: 0.503 AC: 5307 AN: 10550

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34259 AN: 67932

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.483 Hom.: 8729

Bravo AF: 0.519

Asia WGS AF: 0.509 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.67
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3780914; hg19: chr10-45935744; COSMIC: COSV107481571; COSMIC: COSV107481571;