NM_000698.5:c.397C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000698.5(ALOX5):c.397C>T(p.Arg133Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000202 in 1,614,200 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R133H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

ALOX5
NM_000698.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.39

Publications

7 publications found

Variant links:

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]

ALOX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04325679).

BP6

Variant 10-45395902-C-T is Benign according to our data. Variant chr10-45395902-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 741995.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX5	NM_000698.5	MANE Select	c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	NP_000689.1	P09917-1
ALOX5	NM_001320862.2		c.-39C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001307791.1
ALOX5	NM_001320861.2		c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	NP_001307790.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	ENSP00000363512.2	P09917-1
ALOX5	ENST00000542434.5	TSL:1	c.397C>T	p.Arg133Cys	missense	Exon 3 of 13	ENSP00000437634.1	P09917-2
ALOX5	ENST00000851643.1		c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000485

AC:

122

AN:

251474

AF XY:

0.000625

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

212

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.00303

AC:

261

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1112002

Other (OTH)

AF:

0.000232

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000568

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.068

MetaRNN

Benign

0.043

MetaSVM

Uncertain

0.67

MutationAssessor

Uncertain

2.4

PhyloP100

4.4

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.58

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.66

MVP

0.96

MPC

0.59

ClinPred

0.11

GERP RS

6.0

Varity_R

0.52

gMVP

0.74

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over