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GeneBe

10-45440444-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_000698.5(ALOX5):c.996G>A(p.Pro332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ALOX5
NM_000698.5 synonymous

Scores

2

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.451
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.451 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 143 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALOX5NM_000698.5 linkuse as main transcriptc.996G>A p.Pro332= synonymous_variant 8/14 ENST00000374391.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALOX5ENST00000374391.7 linkuse as main transcriptc.996G>A p.Pro332= synonymous_variant 8/141 NM_000698.5 P1P09917-1
ALOX5ENST00000542434.5 linkuse as main transcriptc.996G>A p.Pro332= synonymous_variant 8/131 P09917-2
ALOX5ENST00000475300.1 linkuse as main transcriptn.15G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000940
AC:
143
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00261
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000298
AC:
75
AN:
251364
Hom.:
0
AF XY:
0.000302
AC XY:
41
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.00265
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000116
AC:
170
AN:
1461858
Hom.:
0
Cov.:
32
AF XY:
0.000131
AC XY:
95
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00218
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000649
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000946
AC:
144
AN:
152280
Hom.:
0
Cov.:
33
AF XY:
0.000913
AC XY:
68
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00262
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000549
Hom.:
0
Bravo
AF:
0.00112
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not provided Other:1
not provided, no classification providedliterature onlyFunctional Genomics, Thrombosis Research Institute, India-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
2.7
Dann
Benign
0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146362560; hg19: chr10-45935892; API