10-45445957-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000698.5(ALOX5):c.*270C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 417,270 control chromosomes in the GnomAD database, including 58 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 0.014 (24 hom., cov: 33)
  • Exomes 𝑓: 0.014 (34 hom.)
• Consequence: ALOX5 NM_000698.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd at 2067 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX5	NM_000698.5	c.*270C>T		3_prime_UTR_variant	14/14	ENST00000374391.7
LOC102724323	NR_120674.1	n.180-1105G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5	ENST00000374391.7	c.*270C>T		3_prime_UTR_variant	14/14	1	NM_000698.5	P1
ALOX5	ENST00000542434.5	c.*270C>T		3_prime_UTR_variant	13/13	1
	ENST00000435635.1	n.180-1105G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2067 AN: 152156 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0138 AC: 3659 AN: 264996 Hom.: 34 Cov.: 0 AF XY: 0.0135 AC XY: 1819 AN XY: 135024

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.00842

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0000425

Gnomad4 SAS exome AF: 0.00130

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0136 AC: 2069 AN: 152274 Hom.: 24 Cov.: 33 AF XY: 0.0143 AC XY: 1068 AN XY: 74448

Gnomad4 AFR AF: 0.00975

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00858 Hom.: 3

Bravo AF: 0.0119

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.4
Dann	Benign	0.69

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: rs13134; hg19: chr10-45941405;