dbSNP rs7220870: ALOX15:c.-272G>T (chr17-4641923-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000574640.1(ALOX15):c.-272G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 533,576 control chromosomes in the GnomAD database, including 13,483 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3301 hom., cov: 31)

Exomes 𝑓: 0.23 ( 10182 hom. )

Consequence

ALOX15
ENST00000574640.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.886

Publications

8 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5 link	c.-272G>T		upstream_gene_variant		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.-272G>T		upstream_gene_variant		1	NM_001140.5	ENSP00000293761.3		P16050-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30940

AN:

151782

Hom.:

3296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.225

AC:

85966

AN:

381676

Hom.:

10182

Cov.:

AF XY:

0.231

AC XY:

46411

AN XY:

201298

show subpopulations

African (AFR)

AF:

0.158

AC:

1728

AN:

10916

American (AMR)

AF:

0.243

AC:

3920

AN:

16132

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

3134

AN:

11480

East Asian (EAS)

AF:

0.147

AC:

3565

AN:

24212

South Asian (SAS)

AF:

0.309

AC:

13511

AN:

43674

European-Finnish (FIN)

AF:

0.226

AC:

4927

AN:

21808

Middle Eastern (MID)

AF:

0.258

AC:

423

AN:

1638

European-Non Finnish (NFE)

AF:

0.217

AC:

49828

AN:

230048

Other (OTH)

AF:

0.226

AC:

4930

AN:

21768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3180

6360

9540

12720

15900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.204

AC:

30969

AN:

151900

Hom.:

3301

Cov.:

AF XY:

0.206

AC XY:

15260

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.151

AC:

6265

AN:

41448

American (AMR)

AF:

0.226

AC:

3447

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

886

AN:

3470

East Asian (EAS)

AF:

0.176

AC:

905

AN:

5138

South Asian (SAS)

AF:

0.323

AC:

1558

AN:

4820

European-Finnish (FIN)

AF:

0.238

AC:

2499

AN:

10516

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14780

AN:

67938

Other (OTH)

AF:

0.210

AC:

443

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1239

2479

3718

4958

6197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.171

Hom.:

1193

Bravo

AF:

0.202

Asia WGS

AF:

0.253

AC:

880

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.69

PhyloP100

-0.89

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=296/4

polymorphism (auto)

(source)

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

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

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