chr17-4639422-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001140.5(ALOX15):​c.337+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,605,980 control chromosomes in the GnomAD database, including 58,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 6769 hom., cov: 30)
Exomes 𝑓: 0.28 ( 51719 hom. )

Consequence

ALOX15
NM_001140.5 splice_region, intron

Scores

2
Splicing: ADA: 0.0001208
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04
Variant links:
Genes affected
ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALOX15NM_001140.5 linkc.337+8C>T splice_region_variant, intron_variant Intron 2 of 13 ENST00000293761.8 NP_001131.3 P16050-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALOX15ENST00000293761.8 linkc.337+8C>T splice_region_variant, intron_variant Intron 2 of 13 1 NM_001140.5 ENSP00000293761.3 P16050-1

Frequencies

GnomAD3 genomes
AF:
0.297
AC:
45108
AN:
151712
Hom.:
6768
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.284
Gnomad AMI
AF:
0.208
Gnomad AMR
AF:
0.363
Gnomad ASJ
AF:
0.330
Gnomad EAS
AF:
0.312
Gnomad SAS
AF:
0.248
Gnomad FIN
AF:
0.315
Gnomad MID
AF:
0.175
Gnomad NFE
AF:
0.291
Gnomad OTH
AF:
0.286
GnomAD2 exomes
AF:
0.300
AC:
74030
AN:
246988
AF XY:
0.292
show subpopulations
Gnomad AFR exome
AF:
0.285
Gnomad AMR exome
AF:
0.392
Gnomad ASJ exome
AF:
0.316
Gnomad EAS exome
AF:
0.314
Gnomad FIN exome
AF:
0.317
Gnomad NFE exome
AF:
0.283
Gnomad OTH exome
AF:
0.286
GnomAD4 exome
AF:
0.282
AC:
410191
AN:
1454152
Hom.:
51719
Cov.:
49
AF XY:
0.281
AC XY:
203443
AN XY:
723490
show subpopulations
Gnomad4 AFR exome
AF:
0.272
AC:
9052
AN:
33302
Gnomad4 AMR exome
AF:
0.389
AC:
17314
AN:
44496
Gnomad4 ASJ exome
AF:
0.314
AC:
8185
AN:
26054
Gnomad4 EAS exome
AF:
0.305
AC:
12094
AN:
39618
Gnomad4 SAS exome
AF:
0.241
AC:
20776
AN:
86060
Gnomad4 FIN exome
AF:
0.321
AC:
16888
AN:
52656
Gnomad4 NFE exome
AF:
0.279
AC:
308102
AN:
1106114
Gnomad4 Remaining exome
AF:
0.275
AC:
16556
AN:
60108
Heterozygous variant carriers
0
15272
30544
45816
61088
76360
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
10564
21128
31692
42256
52820
<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:
0.297
AC:
45133
AN:
151828
Hom.:
6769
Cov.:
30
AF XY:
0.298
AC XY:
22139
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.283
AC:
0.283333
AN:
0.283333
Gnomad4 AMR
AF:
0.363
AC:
0.362922
AN:
0.362922
Gnomad4 ASJ
AF:
0.330
AC:
0.329683
AN:
0.329683
Gnomad4 EAS
AF:
0.311
AC:
0.311479
AN:
0.311479
Gnomad4 SAS
AF:
0.249
AC:
0.249166
AN:
0.249166
Gnomad4 FIN
AF:
0.315
AC:
0.314836
AN:
0.314836
Gnomad4 NFE
AF:
0.291
AC:
0.291041
AN:
0.291041
Gnomad4 OTH
AF:
0.285
AC:
0.284834
AN:
0.284834
Heterozygous variant carriers
0
1622
3243
4865
6486
8108
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
448
896
1344
1792
2240
<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:
0.291
Hom.:
24415
Bravo
AF:
0.301
Asia WGS
AF:
0.291
AC:
1011
AN:
3478
EpiCase
AF:
0.277
EpiControl
AF:
0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.73
DANN
Benign
0.86
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00012
dbscSNV1_RF
Benign
0.0040
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs11078528; hg19: chr17-4542717; COSMIC: COSV53396048; COSMIC: COSV53396048; API