Genetic Variant NM_001140.5:c.808-94C>T (chr17-4637352-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.808-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,389,162 control chromosomes in the GnomAD database, including 14,827 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 0.11 ( 1125 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13702 hom. )

Consequence

ALOX15
NM_001140.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.709

Publications

4 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5 link	c.808-94C>T		intron_variant	Intron 6 of 13	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ALOX15	ENST00000293761.8 link	c.808-94C>T	intron_variant	Intron 6 of 13	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6 link	c.808-94C>T	intron_variant	Intron 7 of 14	2		ENSP00000458832.1
ALOX15	ENST00000574640.1 link	c.691-94C>T	intron_variant	Intron 6 of 13	2		ENSP00000460483.1
ALOX15	ENST00000576572.1 link	n.399-94C>T	intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16520

AN:

152058

Hom.:

1124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.142

AC:

175329

AN:

1236986

Hom.:

13702

AF XY:

0.140

AC XY:

84723

AN XY:

605274

show subpopulations

African (AFR)

AF:

0.0222

AC:

616

AN:

27800

American (AMR)

AF:

0.127

AC:

3206

AN:

25168

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

2259

AN:

18852

East Asian (EAS)

AF:

0.000607

AC:

AN:

36236

South Asian (SAS)

AF:

0.0644

AC:

3892

AN:

60396

European-Finnish (FIN)

AF:

0.122

AC:

5646

AN:

46326

Middle Eastern (MID)

AF:

0.122

AC:

618

AN:

5068

European-Non Finnish (NFE)

AF:

0.158

AC:

152390

AN:

965402

Other (OTH)

AF:

0.129

AC:

6680

AN:

51738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6986

13972

20958

27944

34930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5452

10904

16356

21808

27260

<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:

0.109

AC:

16525

AN:

152176

Hom.:

1125

Cov.:

AF XY:

0.106

AC XY:

7893

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0301

AC:

1250

AN:

41514

American (AMR)

AF:

0.137

AC:

2094

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

415

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5186

South Asian (SAS)

AF:

0.0550

AC:

265

AN:

4816

European-Finnish (FIN)

AF:

0.120

AC:

1272

AN:

10588

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10705

AN:

67990

Other (OTH)

AF:

0.133

AC:

281

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

756

1512

2268

3024

3780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.120

Hom.:

217

Bravo

AF:

0.106

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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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