rs11571340

Variant names:

• chr17-7004900-A-G
• rs11571340
• NM_000697.3:c.1162-357A>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.1162-357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,224 control chromosomes in the GnomAD database, including 1,152 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 0.11 (1152 hom., cov: 31)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.1162-357A>G		intron_variant	Intron 8 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.233+4896T>C		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.955-357A>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.1162-357A>G		intron_variant	Intron 8 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16106 AN: 152106 Hom.: 1148 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0931

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

GnomAD4 genome AF: 0.106 AC: 16126 AN: 152224 Hom.: 1152 Cov.: 31 AF XY: 0.111 AC XY: 8272 AN XY: 74440

African (AFR) AF: 0.108 AC: 4473 AN: 41526

American (AMR) AF: 0.259 AC: 3955 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3470

East Asian (EAS) AF: 0.114 AC: 590 AN: 5180

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1601 AN: 10602

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0707 AC: 4811 AN: 68018

Other (OTH) AF: 0.0931 AC: 197 AN: 2116

Alfa AF: 0.0830 Hom.: 2954

Bravo AF: 0.119

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.63
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11571340; hg19: chr17-6908219; COSMIC: COSV52349174; COSMIC: COSV52349174;