rs2619118

Variant names:

• chr17-4636982-C-T
• rs2619118
• NM_001140.5:c.951+133G>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.951+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,088,368 control chromosomes in the GnomAD database, including 141,648 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 0.44 (15723 hom., cov: 32)
  • Exomes 𝑓: 0.51 (125925 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.951+133G>A		intron_variant	Intron 7 of 13	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.951+133G>A		intron_variant	Intron 7 of 13	1	NM_001140.5	ENSP00000293761.3
ALOX15	ENST00000570836.6	c.951+133G>A		intron_variant	Intron 8 of 14	2		ENSP00000458832.1
ALOX15	ENST00000574640.1	c.834+133G>A		intron_variant	Intron 7 of 13	2		ENSP00000460483.1
ALOX15	ENST00000576572.1	n.*188G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66470 AN: 151888 Hom.: 15721 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.515 AC: 481940 AN: 936360 Hom.: 125925 AF XY: 0.518 AC XY: 244162 AN XY: 471640

African (AFR) AF: 0.244 AC: 5393 AN: 22124

American (AMR) AF: 0.377 AC: 10648 AN: 28246

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 8042 AN: 17332

East Asian (EAS) AF: 0.488 AC: 17684 AN: 36272

South Asian (SAS) AF: 0.573 AC: 33353 AN: 58180

European-Finnish (FIN) AF: 0.550 AC: 22829 AN: 41544

Middle Eastern (MID) AF: 0.497 AC: 1444 AN: 2904

European-Non Finnish (NFE) AF: 0.526 AC: 361521 AN: 687726

Other (OTH) AF: 0.500 AC: 21026 AN: 42032

GnomAD4 genome AF: 0.437 AC: 66487 AN: 152008 Hom.: 15723 Cov.: 32 AF XY: 0.441 AC XY: 32737 AN XY: 74280

African (AFR) AF: 0.253 AC: 10477 AN: 41484

American (AMR) AF: 0.400 AC: 6101 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3466

East Asian (EAS) AF: 0.468 AC: 2415 AN: 5164

South Asian (SAS) AF: 0.569 AC: 2739 AN: 4812

European-Finnish (FIN) AF: 0.560 AC: 5899 AN: 10532

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35712 AN: 67974

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.470 Hom.: 2407

Bravo AF: 0.417

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		0.17
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: rs2619118; hg19: chr17-4540277; COSMIC: COSV53398938; COSMIC: COSV53398938;