Menu
GeneBe

10-45382650-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000698.5(ALOX5):c.318C>T(p.Gly106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,613,720 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 Benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ALOX5
NM_000698.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-45382650-C-T is Benign according to our data. Variant chr10-45382650-C-T is described in ClinVar as [Benign]. Clinvar id is 713947.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-2.27 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 59 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALOX5NM_000698.5 linkuse as main transcriptc.318C>T p.Gly106= synonymous_variant 2/14 ENST00000374391.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALOX5ENST00000374391.7 linkuse as main transcriptc.318C>T p.Gly106= synonymous_variant 2/141 NM_000698.5 P1P09917-1
ALOX5ENST00000542434.5 linkuse as main transcriptc.318C>T p.Gly106= synonymous_variant 2/131 P09917-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000388
AC:
59
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00961
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000872
AC:
218
AN:
250060
Hom.:
0
AF XY:
0.000865
AC XY:
117
AN XY:
135214
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.0106
Gnomad SAS exome
AF:
0.000197
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000276
AC:
404
AN:
1461374
Hom.:
0
Cov.:
33
AF XY:
0.000272
AC XY:
198
AN XY:
726954
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000651
Gnomad4 EAS exome
AF:
0.00839
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000387
AC:
59
AN:
152346
Hom.:
0
Cov.:
33
AF XY:
0.000416
AC XY:
31
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00963
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000502
Hom.:
0
Bravo
AF:
0.000404
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
1.4
Dann
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs150281723; hg19: chr10-45878098; COSMIC: COSV100980053; API