NM_001140.5:c.1642-34T>C

Variant names:

• chr17-4632090-A-G
• rs2619112
• NM_001140.5:c.1642-34T>C

Variant summary

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

The NM_001140.5(ALOX15):​c.1642-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,608,558 control chromosomes in the GnomAD database, including 229,305 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 0.54 (22061 hom., cov: 33)
  • Exomes 𝑓: 0.53 (207244 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 38 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 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.1642-34T>C		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.1642-34T>C		intron	N/A	ENSP00000293761.3
	ALOX15	ENST00000570836.6	TSL:2	c.1642-34T>C		intron	N/A	ENSP00000458832.1
	ALOX15	ENST00000574640.1	TSL:2	c.1525-34T>C		intron	N/A	ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81791 AN: 151990 Hom.: 22051 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.522

GnomAD2 exomes AF: 0.530 AC: 131182 AN: 247592 AF XY: 0.531

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.533

GnomAD4 exome AF: 0.533 AC: 775964 AN: 1456450 Hom.: 207244 Cov.: 50 AF XY: 0.532 AC XY: 385259 AN XY: 723680

African (AFR) AF: 0.574 AC: 19169 AN: 33398

American (AMR) AF: 0.489 AC: 21739 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 11750 AN: 25826

East Asian (EAS) AF: 0.587 AC: 23225 AN: 39598

South Asian (SAS) AF: 0.536 AC: 46026 AN: 85798

European-Finnish (FIN) AF: 0.534 AC: 28331 AN: 53038

Middle Eastern (MID) AF: 0.563 AC: 3240 AN: 5752

European-Non Finnish (NFE) AF: 0.533 AC: 590342 AN: 1108398

Other (OTH) AF: 0.534 AC: 32142 AN: 60172

GnomAD4 genome AF: 0.538 AC: 81832 AN: 152108 Hom.: 22061 Cov.: 33 AF XY: 0.539 AC XY: 40051 AN XY: 74362

African (AFR) AF: 0.567 AC: 23551 AN: 41500

American (AMR) AF: 0.497 AC: 7603 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2998 AN: 5166

South Asian (SAS) AF: 0.540 AC: 2604 AN: 4824

European-Finnish (FIN) AF: 0.546 AC: 5780 AN: 10588

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35971 AN: 67952

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.532 Hom.: 33040

Bravo AF: 0.540

Asia WGS AF: 0.541 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.073
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: rs2619112; hg19: chr17-4535385; COSMIC: COSV53400348;