dbSNP rs2664593: ALOX15:c.-186G>C (chr17-4641837-C-G) – 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.-186G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 726,100 control chromosomes in the GnomAD database, including 16,093 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 0.19 ( 2953 hom., cov: 31)

Exomes 𝑓: 0.21 ( 13140 hom. )

Consequence

ALOX15
ENST00000574640.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

Publications

17 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5 link	c.-186G>C		upstream_gene_variant		ENST00000293761.8	NP_001131.3	P16050-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALOX15	ENST00000574640.1 link	c.-186G>C	5_prime_UTR_variant	Exon 1 of 14	2		ENSP00000460483.1	P16050-2
ALOX15	ENST00000570836.6 link	c.-25-161G>C	intron_variant	Intron 1 of 14	2		ENSP00000458832.1	P16050-1
ALOX15	ENST00000293761.8 link	c.-186G>C	upstream_gene_variant		1	NM_001140.5	ENSP00000293761.3	P16050-1
ALOX15	ENST00000573740.1 link	n.-159G>C	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29028

AN:

151818

Hom.:

2947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.207

AC:

118959

AN:

574164

Hom.:

13140

Cov.:

AF XY:

0.211

AC XY:

62423

AN XY:

296252

show subpopulations

African (AFR)

AF:

0.125

AC:

1824

AN:

14594

American (AMR)

AF:

0.231

AC:

4481

AN:

19400

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

2963

AN:

14570

East Asian (EAS)

AF:

0.155

AC:

4902

AN:

31666

South Asian (SAS)

AF:

0.276

AC:

13367

AN:

48390

European-Finnish (FIN)

AF:

0.224

AC:

7134

AN:

31862

Middle Eastern (MID)

AF:

0.185

AC:

411

AN:

2226

European-Non Finnish (NFE)

AF:

0.204

AC:

77700

AN:

381452

Other (OTH)

AF:

0.206

AC:

6177

AN:

30004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4595

9191

13786

18382

22977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.191

AC:

29055

AN:

151936

Hom.:

2953

Cov.:

AF XY:

0.193

AC XY:

14355

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.126

AC:

5238

AN:

41456

American (AMR)

AF:

0.212

AC:

3243

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3466

East Asian (EAS)

AF:

0.179

AC:

922

AN:

5144

South Asian (SAS)

AF:

0.294

AC:

1409

AN:

4794

European-Finnish (FIN)

AF:

0.237

AC:

2498

AN:

10536

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14468

AN:

67942

Other (OTH)

AF:

0.188

AC:

398

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1160

2321

3481

4642

5802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.197

Hom.:

423

Bravo

AF:

0.187

Asia WGS

AF:

0.232

AC:

806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.3

(source)

DANN

Benign

0.44

PhyloP100

-0.17

PromoterAI

0.0096

Neutral

(source)

Mutation Taster

=299/1

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

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rs2664593

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