10-45421928-C-T

Variant names:

• chr10-45421928-C-T
• rs3780901
• NM_000698.5:c.555-2113C>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.555-2113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,120 control chromosomes in the GnomAD database, including 33,948 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 0.66 (33948 hom., cov: 33)
• Consequence: ALOX5 NM_000698.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5	c.555-2113C>T		intron_variant	Intron 4 of 13	ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7	c.555-2113C>T		intron_variant	Intron 4 of 13	1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5	c.555-2113C>T		intron_variant	Intron 4 of 12	1		ENSP00000437634.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100874 AN: 152002 Hom.: 33930 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.663 AC: 100928 AN: 152120 Hom.: 33948 Cov.: 33 AF XY: 0.664 AC XY: 49414 AN XY: 74370

African (AFR) AF: 0.594 AC: 24642 AN: 41474

American (AMR) AF: 0.707 AC: 10820 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1830 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4059 AN: 5146

South Asian (SAS) AF: 0.526 AC: 2539 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8086 AN: 10612

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46780 AN: 67988

Other (OTH) AF: 0.642 AC: 1353 AN: 2106

Alfa AF: 0.675 Hom.: 97542

Bravo AF: 0.659

Asia WGS AF: 0.648 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.26
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs3780901; hg19: chr10-45917376;