chr10-45445957-C-T

Variant names:

• chr10-45445957-C-T
• rs13134
• NM_000698.5:c.*270C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000231964 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd4 at 2069 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.*270C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.*270C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.*270C>T		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000437634.1
ENSG00000231964	ENST00000435635.1	n.180-1105G>A		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.0128 AC: 110 AN: 8610

American (AMR) AF: 0.00842 AC: 82 AN: 9736

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 209 AN: 9660

East Asian (EAS) AF: 0.0000425 AC: 1 AN: 23506

South Asian (SAS) AF: 0.00130 AC: 9 AN: 6900

European-Finnish (FIN) AF: 0.0315 AC: 638 AN: 20260

Middle Eastern (MID) AF: 0.0117 AC: 16 AN: 1368

European-Non Finnish (NFE) AF: 0.0142 AC: 2382 AN: 167730

Other (OTH) AF: 0.0123 AC: 212 AN: 17226

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

African (AFR) AF: 0.00975 AC: 405 AN: 41556

American (AMR) AF: 0.0142 AC: 218 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0294 AC: 312 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 981 AN: 68022

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0134 Hom.: 25

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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: rs13134; hg19: chr10-45941405;