17-4631539-A-G

Variant names:

• chr17-4631539-A-G
• rs916055
• NM_001140.5:c.*61T>C

Variant summary

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

The NM_001140.5(ALOX15):​c.*61T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,587,468 control chromosomes in the GnomAD database, including 89,302 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 0.31 (7566 hom., cov: 31)
  • Exomes 𝑓: 0.33 (81736 hom.)
• Consequence: ALOX15 NM_001140.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 25 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 (AMR) allele frequency at 95% confidence interval = 0.386 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	NM_001140.5	MANE Select	c.*61T>C		3_prime_UTR	Exon 14 of 14	NP_001131.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.*61T>C		3_prime_UTR	Exon 14 of 14	ENSP00000293761.3
	ALOX15	ENST00000570836.6	TSL:2	c.*61T>C		3_prime_UTR	Exon 15 of 15	ENSP00000458832.1
	ALOX15	ENST00000574640.1	TSL:2	c.*61T>C		3_prime_UTR	Exon 14 of 14	ENSP00000460483.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46412 AN: 151850 Hom.: 7561 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.335 AC: 480203 AN: 1435500 Hom.: 81736 Cov.: 30 AF XY: 0.336 AC XY: 239491 AN XY: 712318

African (AFR) AF: 0.183 AC: 6079 AN: 33238

American (AMR) AF: 0.414 AC: 17974 AN: 43364

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10289 AN: 24804

East Asian (EAS) AF: 0.407 AC: 16104 AN: 39528

South Asian (SAS) AF: 0.360 AC: 29684 AN: 82460

European-Finnish (FIN) AF: 0.366 AC: 17623 AN: 48188

Middle Eastern (MID) AF: 0.299 AC: 1222 AN: 4086

European-Non Finnish (NFE) AF: 0.329 AC: 361592 AN: 1100314

Other (OTH) AF: 0.330 AC: 19636 AN: 59518

GnomAD4 genome AF: 0.306 AC: 46437 AN: 151968 Hom.: 7566 Cov.: 31 AF XY: 0.309 AC XY: 22977 AN XY: 74278

African (AFR) AF: 0.188 AC: 7791 AN: 41476

American (AMR) AF: 0.394 AC: 6024 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3466

East Asian (EAS) AF: 0.389 AC: 2002 AN: 5144

South Asian (SAS) AF: 0.361 AC: 1740 AN: 4818

European-Finnish (FIN) AF: 0.355 AC: 3745 AN: 10536

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22706 AN: 67948

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.317 Hom.: 13213

Bravo AF: 0.299

Asia WGS AF: 0.372 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.87
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: rs916055; hg19: chr17-4534834; COSMIC: COSV53396759;