rs34210653

chr17-4632019-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (47 hom., cov: 33)
  • Exomes 𝑓: 0.020 (612 hom.)
• Consequence: ALOX15 NM_001140.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.21

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]

ACMG classification

Verdict is Benign. Variant got -13 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 id is 624559.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX15	NM_001140.5	c.1679C>T	p.Thr560Met	missense_variant	13/14	ENST00000293761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000293761.8	c.1679C>T	p.Thr560Met	missense_variant	13/14	1	NM_001140.5	P1
ALOX15	ENST00000570836.6	c.1679C>T	p.Thr560Met	missense_variant	14/15	2		P1
ALOX15	ENST00000574640.1	c.1562C>T	p.Thr521Met	missense_variant	13/14	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

GnomAD3 exomes AF: 0.0274 AC: 6861 AN: 250268 Hom.: 339 AF XY: 0.0235 AC XY: 3181 AN XY: 135222

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 SAS exome AF: 0.00969

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

Gnomad4 AFR exome AF: 0.00335

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.00705

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00974

Gnomad4 FIN exome AF: 0.00782

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0167

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

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0160 Hom.: 36

Bravo AF: 0.0213

TwinsUK AF: 0.0183 AC: 68

ALSPAC AF: 0.0161 AC: 62

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.0167 AC: 144

ExAC AF: 0.0229 AC: 2785

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0141

EpiControl AF: 0.0146

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Asthma, nasal polyps, and aspirin intolerance Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

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;D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.3	M;M;.
MutationTaster	Benign	0.76	D;D;D;D
PrimateAI	Benign	0.48	T
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.19
MPC		0.73
ClinPred		0.047	T
GERP RS		3.4
Varity_R		0.65
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs34210653; hg19: chr17-4535314; COSMIC: COSV53398011;