rs7220870

Positions:

• chr17-4641923-C-A
• chr17-4641923-C-G
• chr17-4641923-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000574640.1(ALOX15):​c.-272G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 533,576 control chromosomes in the GnomAD database, including 13,483 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 0.20 (3301 hom., cov: 31)
  • Exomes 𝑓: 0.23 (10182 hom.)
• Consequence: ALOX15 ENST00000574640.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.4641923C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000574640.1	c.-272G>T		5_prime_UTR_premature_start_codon_gain_variant	1/14	2		ENSP00000460483.1
ALOX15	ENST00000574640.1	c.-272G>T		5_prime_UTR_variant	1/14	2		ENSP00000460483.1
ALOX15	ENST00000570836.6	c.-25-247G>T		intron_variant		2		ENSP00000458832.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30940 AN: 151782 Hom.: 3296 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.225 AC: 85966 AN: 381676 Hom.: 10182 Cov.: 4 AF XY: 0.231 AC XY: 46411 AN XY: 201298

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.204 AC: 30969 AN: 151900 Hom.: 3301 Cov.: 31 AF XY: 0.206 AC XY: 15260 AN XY: 74208

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.210

Alfa AF: 0.157 Hom.: 549

Bravo AF: 0.202

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7220870; hg19: chr17-4545218;