dbSNP rs11078528: ALOX15:c.337+8C>T (chr17-4639422-G-A) – ACMG Classification: Benign (-12 pts)

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

Splicing: ADA: 0.0001208

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

12 publications found

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]

ALOX15 Gene-Disease associations (from GenCC):

pregnancy loss, recurrent, susceptibility
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ALOX15 links:

Genome browser will be placed here

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
ALOX15	NM_001140.5 link	c.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
ALOX15	ENST00000293761.8 link	c.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.:

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.:

AF XY:

0.281

AC XY:

203443

AN XY:

723490

show subpopulations

African (AFR)

AF:

0.272

AC:

9052

AN:

33302

American (AMR)

AF:

0.389

AC:

17314

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

8185

AN:

26054

East Asian (EAS)

AF:

0.305

AC:

12094

AN:

39618

South Asian (SAS)

AF:

0.241

AC:

20776

AN:

86060

European-Finnish (FIN)

AF:

0.321

AC:

16888

AN:

52656

Middle Eastern (MID)

AF:

0.213

AC:

1224

AN:

5744

European-Non Finnish (NFE)

AF:

0.279

AC:

308102

AN:

1106114

Other (OTH)

AF:

0.275

AC:

16556

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15272

30544

45816

61088

76360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.297

AC:

45133

AN:

151828

Hom.:

6769

Cov.:

AF XY:

0.298

AC XY:

22139

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.283

AC:

11726

AN:

41386

American (AMR)

AF:

0.363

AC:

5544

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1144

AN:

3470

East Asian (EAS)

AF:

0.311

AC:

1601

AN:

5140

South Asian (SAS)

AF:

0.249

AC:

1195

AN:

4796

European-Finnish (FIN)

AF:

0.315

AC:

3319

AN:

10542

Middle Eastern (MID)

AF:

0.171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19764

AN:

67908

Other (OTH)

AF:

0.285

AC:

601

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1622

3243

4865

6486

8108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.86

PhyloP100

-2.0

PromoterAI

0.0094

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11078528

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over