rs11568070

Variant names:

• chr17-4641943-G-A
• rs11568070
• ENST00000570836.6:c.-25-267C>T

Variant summary

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

The ENST00000570836.6(ALOX15):​c.-25-267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 494,280 control chromosomes in the GnomAD database, including 188 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 0.020 (52 hom., cov: 31)
  • Exomes 𝑓: 0.020 (136 hom.)
• Consequence: ALOX15 ENST00000570836.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 17 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=-0.8).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570836.6. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000570836.6	TSL:2	c.-25-267C>T		intron	N/A	ENSP00000458832.1
	ALOX15	ENST00000574640.1	TSL:2	c.-292C>T		upstream_gene	N/A	ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2996 AN: 152140 Hom.: 50 Cov.: 31

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.0204 AC: 6988 AN: 342020 Hom.: 136 Cov.: 4 AF XY: 0.0217 AC XY: 3929 AN XY: 181160

African (AFR) AF: 0.0256 AC: 256 AN: 9992

American (AMR) AF: 0.0177 AC: 265 AN: 14972

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 810 AN: 10098

East Asian (EAS) AF: 0.000683 AC: 14 AN: 20502

South Asian (SAS) AF: 0.0350 AC: 1535 AN: 43808

European-Finnish (FIN) AF: 0.00326 AC: 58 AN: 17792

Middle Eastern (MID) AF: 0.0738 AC: 106 AN: 1436

European-Non Finnish (NFE) AF: 0.0169 AC: 3457 AN: 204122

Other (OTH) AF: 0.0252 AC: 487 AN: 19298

GnomAD4 genome AF: 0.0197 AC: 3002 AN: 152260 Hom.: 52 Cov.: 31 AF XY: 0.0193 AC XY: 1436 AN XY: 74460

African (AFR) AF: 0.0241 AC: 1003 AN: 41540

American (AMR) AF: 0.0225 AC: 345 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4820

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1102 AN: 68010

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0241 Hom.: 4

Bravo AF: 0.0212

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.26
PromoterAI		0.15	Neutral
Mutation Taster		=100/0	polymorphism

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: rs11568070; hg19: chr17-4545238;