rs2292350

Variant names:

• chr17-6998353-G-A
• rs2292350
• NM_000697.3:c.338-156G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000697.3(ALOX12):​c.338-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,010 control chromosomes in the GnomAD database, including 9,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (9266 hom., cov: 31)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640
• Publications: 20 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-6998353-G-A is Benign according to our data. Variant chr17-6998353-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.338-156G>A		intron_variant	Intron 2 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.233+11443C>T		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.338-156G>A		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.338-156G>A		intron_variant	Intron 2 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48982 AN: 151892 Hom.: 9265 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.322 AC: 48986 AN: 152010 Hom.: 9266 Cov.: 31 AF XY: 0.324 AC XY: 24042 AN XY: 74268

African (AFR) AF: 0.113 AC: 4682 AN: 41490

American (AMR) AF: 0.314 AC: 4801 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2077 AN: 5160

South Asian (SAS) AF: 0.356 AC: 1714 AN: 4814

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10546

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28613 AN: 67946

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.394 Hom.: 52833

Bravo AF: 0.300

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		0.064
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: rs2292350; hg19: chr17-6901672; COSMIC: COSV52350339; COSMIC: COSV52350339;