rs312470

chr17-6998860-G-Achr17-6998860-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000697.3(ALOX12):c.542+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,613,954 control chromosomes in the GnomAD database, including 659,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (52833 hom., cov: 31)
  • Exomes 𝑓: 0.91 (606628 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-6998860-G-A is Benign according to our data. Variant chr17-6998860-G-A is described in ClinVar as [Benign]. Clinvar id is 1262104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.542+23G>A		intron_variant		ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.233+10936C>T		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.542+23G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.542+23G>A		intron_variant		1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+13336C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125256 AN: 152012 Hom.: 52812 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.852

GnomAD3 exomes AF: 0.847 AC: 212795 AN: 251286 Hom.: 93297 AF XY: 0.869 AC XY: 118057 AN XY: 135826

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.941

Gnomad EAS exome AF: 0.878

Gnomad SAS exome AF: 0.958

Gnomad FIN exome AF: 0.856

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.907 AC: 1325798 AN: 1461824 Hom.: 606628 Cov.: 61 AF XY: 0.911 AC XY: 662537 AN XY: 727218

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.939

Gnomad4 EAS exome AF: 0.881

Gnomad4 SAS exome AF: 0.957

Gnomad4 FIN exome AF: 0.861

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.824 AC: 125322 AN: 152130 Hom.: 52833 Cov.: 31 AF XY: 0.821 AC XY: 61030 AN XY: 74380

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.853

Alfa AF: 0.858 Hom.: 12075

Bravo AF: 0.796

Asia WGS AF: 0.873 AC: 3037 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	-0.83
Cadd	Benign	6.3
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs312470; hg19: chr17-6902179; COSMIC: COSV52352443; COSMIC: COSV52352443;