17-4636097-C-G

Variant names:

• chr17-4636097-C-G
• rs7217186
• NM_001140.5:c.952-129G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001140.5(ALOX15):​c.952-129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 809,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.952-129G>C		intron	N/A	NP_001131.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.952-129G>C		intron	N/A	ENSP00000293761.3
	ALOX15	ENST00000570836.6	TSL:2	c.952-129G>C		intron	N/A	ENSP00000458832.1
	ALOX15	ENST00000574640.1	TSL:2	c.835-129G>C		intron	N/A	ENSP00000460483.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000123 AC: 1 AN: 809976 Hom.: 0 AF XY: 0.00000244 AC XY: 1 AN XY: 409946

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19760

American (AMR) AF: 0.0000363 AC: 1 AN: 27550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17300

East Asian (EAS) AF: 0.00 AC: 0 AN: 32772

South Asian (SAS) AF: 0.00 AC: 0 AN: 56778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 576126

Other (OTH) AF: 0.00 AC: 0 AN: 38094

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.43
PhyloP100		-3.7

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: rs7217186; hg19: chr17-4539392;