chr17-7008372-G-A

Variant names:

• chr17-7008372-G-A
• rs11571364
• NM_000697.3:c.1541-1375G>A

Variant summary

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

The NM_000697.3(ALOX12):​c.1541-1375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,266 control chromosomes in the GnomAD database, including 212 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 0.045 (212 hom., cov: 32)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 4 publications found

Genes affected

ALOX12 (HGNC:429): (arachidonate 12-lipoxygenase, 12S type) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.1541-1375G>A		intron_variant	Intron 11 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.233+1424C>T		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.1334-1375G>A		intron_variant	Intron 10 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.1541-1375G>A		intron_variant	Intron 11 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6784 AN: 152148 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0445 AC: 6782 AN: 152266 Hom.: 212 Cov.: 32 AF XY: 0.0425 AC XY: 3165 AN XY: 74460

African (AFR) AF: 0.0127 AC: 529 AN: 41544

American (AMR) AF: 0.0581 AC: 889 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4832

European-Finnish (FIN) AF: 0.0380 AC: 403 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0653 AC: 4438 AN: 68012

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0519 Hom.: 131

Bravo AF: 0.0459

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		1.8
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: rs11571364; hg19: chr17-6911691;