17-7003751-A-G

Variant names:

• chr17-7003751-A-G
• rs2920421
• NM_000697.3:c.1162-1506A>G

Variant summary

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

The NM_000697.3(ALOX12):​c.1162-1506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,098 control chromosomes in the GnomAD database, including 35,664 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 0.68 (35664 hom., cov: 33)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.1162-1506A>G		intron_variant	Intron 8 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.233+6045T>C		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.955-1506A>G		intron_variant	Intron 7 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.1162-1506A>G		intron_variant	Intron 8 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103844 AN: 151980 Hom.: 35640 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.683 AC: 103923 AN: 152098 Hom.: 35664 Cov.: 33 AF XY: 0.688 AC XY: 51157 AN XY: 74350

African (AFR) AF: 0.646 AC: 26774 AN: 41474

American (AMR) AF: 0.742 AC: 11330 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2376 AN: 3470

East Asian (EAS) AF: 0.669 AC: 3459 AN: 5174

South Asian (SAS) AF: 0.771 AC: 3727 AN: 4832

European-Finnish (FIN) AF: 0.713 AC: 7528 AN: 10560

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46385 AN: 67998

Other (OTH) AF: 0.681 AC: 1437 AN: 2110

Alfa AF: 0.684 Hom.: 79673

Bravo AF: 0.681

Asia WGS AF: 0.702 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.55
PhyloP100		-0.55
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: rs2920421; hg19: chr17-6907070; COSMIC: COSV52351789; COSMIC: COSV52351789;