NM_001140.5:c.808-94C>T

Variant names:

• chr17-4637352-G-A
• rs11078527
• NM_001140.5:c.808-94C>T

Variant summary

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

The NM_001140.5(ALOX15):​c.808-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,389,162 control chromosomes in the GnomAD database, including 14,827 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 0.11 (1125 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13702 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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.808-94C>T		intron	N/A	NP_001131.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.808-94C>T		intron	N/A	ENSP00000293761.3	P16050-1
	ALOX15	ENST00000570836.6	TSL:2	c.808-94C>T		intron	N/A	ENSP00000458832.1	P16050-1
	ALOX15	ENST00000574640.1	TSL:2	c.691-94C>T		intron	N/A	ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16520 AN: 152058 Hom.: 1124 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.142 AC: 175329 AN: 1236986 Hom.: 13702 AF XY: 0.140 AC XY: 84723 AN XY: 605274

African (AFR) AF: 0.0222 AC: 616 AN: 27800

American (AMR) AF: 0.127 AC: 3206 AN: 25168

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2259 AN: 18852

East Asian (EAS) AF: 0.000607 AC: 22 AN: 36236

South Asian (SAS) AF: 0.0644 AC: 3892 AN: 60396

European-Finnish (FIN) AF: 0.122 AC: 5646 AN: 46326

Middle Eastern (MID) AF: 0.122 AC: 618 AN: 5068

European-Non Finnish (NFE) AF: 0.158 AC: 152390 AN: 965402

Other (OTH) AF: 0.129 AC: 6680 AN: 51738

GnomAD4 genome AF: 0.109 AC: 16525 AN: 152176 Hom.: 1125 Cov.: 32 AF XY: 0.106 AC XY: 7893 AN XY: 74400

African (AFR) AF: 0.0301 AC: 1250 AN: 41514

American (AMR) AF: 0.137 AC: 2094 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4816

European-Finnish (FIN) AF: 0.120 AC: 1272 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10705 AN: 67990

Other (OTH) AF: 0.133 AC: 281 AN: 2108

Alfa AF: 0.120 Hom.: 217

Bravo AF: 0.106

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		0.71
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs11078527; hg19: chr17-4540647;