17-4636097-C-T

Variant names:

• chr17-4636097-C-T
• rs7217186
• NM_001140.5:c.952-129G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001140.5(ALOX15):​c.952-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 960,116 control chromosomes in the GnomAD database, including 126,791 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 0.45 (16552 hom., cov: 31)
  • Exomes 𝑓: 0.52 (110239 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75
• Publications: 18 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	NM_001140.5	MANE Select	c.952-129G>A		intron	N/A	NP_001131.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.952-129G>A		intron	N/A	ENSP00000293761.3
	ALOX15	ENST00000570836.6	TSL:2	c.952-129G>A		intron	N/A	ENSP00000458832.1
	ALOX15	ENST00000574640.1	TSL:2	c.835-129G>A		intron	N/A	ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68618 AN: 151894 Hom.: 16551 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.517 AC: 417405 AN: 808104 Hom.: 110239 AF XY: 0.519 AC XY: 212351 AN XY: 409052

African (AFR) AF: 0.277 AC: 5461 AN: 19736

American (AMR) AF: 0.417 AC: 11479 AN: 27536

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 7970 AN: 17278

East Asian (EAS) AF: 0.600 AC: 19660 AN: 32754

South Asian (SAS) AF: 0.566 AC: 32125 AN: 56730

European-Finnish (FIN) AF: 0.552 AC: 21444 AN: 38832

Middle Eastern (MID) AF: 0.490 AC: 1333 AN: 2718

European-Non Finnish (NFE) AF: 0.520 AC: 298708 AN: 574488

Other (OTH) AF: 0.505 AC: 19225 AN: 38032

GnomAD4 genome AF: 0.451 AC: 68630 AN: 152012 Hom.: 16552 Cov.: 31 AF XY: 0.455 AC XY: 33783 AN XY: 74310

African (AFR) AF: 0.285 AC: 11826 AN: 41474

American (AMR) AF: 0.415 AC: 6338 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3192 AN: 5144

South Asian (SAS) AF: 0.575 AC: 2771 AN: 4816

European-Finnish (FIN) AF: 0.559 AC: 5920 AN: 10582

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35427 AN: 67932

Other (OTH) AF: 0.456 AC: 965 AN: 2114

Alfa AF: 0.460 Hom.: 5441

Bravo AF: 0.435

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.66
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs7217186; hg19: chr17-4539392; COSMIC: COSV53400369; COSMIC: COSV53400369;