17-6997526-C-T

Variant names:

• chr17-6997526-C-T
• rs10852889
• NM_000697.3:c.337+499C>T

Variant summary

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

The NM_000697.3(ALOX12):​c.337+499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 149,824 control chromosomes in the GnomAD database, including 25,329 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 0.58 (25329 hom., cov: 27)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65
• Publications: 15 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.337+499C>T		intron_variant	Intron 2 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.234-11986G>A		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.337+499C>T		intron_variant	Intron 2 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.337+499C>T		intron_variant	Intron 2 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.580 AC: 86828 AN: 149720 Hom.: 25309 Cov.: 27

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.555

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.580 AC: 86892 AN: 149824 Hom.: 25329 Cov.: 27 AF XY: 0.584 AC XY: 42574 AN XY: 72932

African (AFR) AF: 0.547 AC: 22211 AN: 40568

American (AMR) AF: 0.650 AC: 9755 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3464

East Asian (EAS) AF: 0.522 AC: 2638 AN: 5056

South Asian (SAS) AF: 0.540 AC: 2567 AN: 4758

European-Finnish (FIN) AF: 0.663 AC: 6576 AN: 9914

Middle Eastern (MID) AF: 0.559 AC: 161 AN: 288

European-Non Finnish (NFE) AF: 0.582 AC: 39434 AN: 67784

Other (OTH) AF: 0.569 AC: 1187 AN: 2086

Alfa AF: 0.534 Hom.: 3782

Bravo AF: 0.575

Asia WGS AF: 0.516 AC: 1798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-4.7
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: rs10852889; hg19: chr17-6900845; COSMIC: COSV52349120; COSMIC: COSV52349120;