rs34210653

Variant names:

• chr17-4632019-G-A
• rs34210653
• NM_001140.5:c.1679C>T
• ALOX15 p.Thr560Met

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001140.5(ALOX15):​c.1679C>T​(p.Thr560Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,613,394 control chromosomes in the GnomAD database, including 659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (47 hom., cov: 33)
  • Exomes 𝑓: 0.020 (612 hom.)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.21
• Publications: 48 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038241744).
• BP6: Variant 17-4632019-G-A is Benign according to our data. Variant chr17-4632019-G-A is described in ClinVar as Benign. ClinVar VariationId is 624559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.061 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	NM_001140.5	MANE Select	c.1679C>T	p.Thr560Met	missense	Exon 13 of 14	NP_001131.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.1679C>T	p.Thr560Met	missense	Exon 13 of 14	ENSP00000293761.3	P16050-1
	ALOX15	ENST00000570836.6	TSL:2	c.1679C>T	p.Thr560Met	missense	Exon 14 of 15	ENSP00000458832.1	P16050-1
	ALOX15	ENST00000574640.1	TSL:2	c.1562C>T	p.Thr521Met	missense	Exon 13 of 14	ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2578 AN: 152174 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0274 AC: 6861 AN: 250268 AF XY: 0.0235

Gnomad AFR exome AF: 0.00381

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.00630

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00794

Gnomad NFE exome AF: 0.0169

Gnomad OTH exome AF: 0.0183

GnomAD4 exome AF: 0.0203 AC: 29658 AN: 1461102 Hom.: 612 Cov.: 33 AF XY: 0.0194 AC XY: 14092 AN XY: 726768

African (AFR) AF: 0.00335 AC: 112 AN: 33478

American (AMR) AF: 0.113 AC: 5035 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00705 AC: 184 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00974 AC: 839 AN: 86116

European-Finnish (FIN) AF: 0.00782 AC: 416 AN: 53182

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.0198 AC: 22038 AN: 1111756

Other (OTH) AF: 0.0167 AC: 1006 AN: 60368

GnomAD4 genome AF: 0.0169 AC: 2579 AN: 152292 Hom.: 47 Cov.: 33 AF XY: 0.0167 AC XY: 1242 AN XY: 74462

African (AFR) AF: 0.00486 AC: 202 AN: 41572

American (AMR) AF: 0.0643 AC: 984 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4828

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1177 AN: 68022

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.0168 Hom.: 94

Bravo AF: 0.0213

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0141

EpiControl AF: 0.0146

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Asthma, nasal polyps, and aspirin intolerance (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0038	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.2
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.65
gMVP		0.42
Mutation Taster		=95/5	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34210653;

hg19: chr17-4535314;

COSMIC: COSV53398011;