17-6997125-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000697.3(ALOX12):c.337+98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,442,712 control chromosomes in the GnomAD database, including 245,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28846 hom., cov: 31)
  • Exomes 𝑓: 0.58 (216515 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.369

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]

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-6997125-T-G is Benign according to our data. Variant chr17-6997125-T-G is described in ClinVar as [Benign]. Clinvar id is 1262015.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.337+98T>G		intron_variant		ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.234-11585A>C		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.337+98T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.337+98T>G		intron_variant		1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+15071A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93218 AN: 151818 Hom.: 28809 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.578 AC: 745693 AN: 1290776 Hom.: 216515 Cov.: 39 AF XY: 0.577 AC XY: 360844 AN XY: 625762

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.614 AC: 93304 AN: 151936 Hom.: 28846 Cov.: 31 AF XY: 0.617 AC XY: 45816 AN XY: 74250

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.592

Alfa AF: 0.581 Hom.: 37369

Bravo AF: 0.615

Asia WGS AF: 0.542 AC: 1891 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	16
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070590; hg19: chr17-6900444; COSMIC: COSV52349106; COSMIC: COSV52349106;