17-6996310-C-T

Position:

• chr17-6996310-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000697.3(ALOX12):​c.135+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,219,326 control chromosomes in the GnomAD database, including 203,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26401 hom., cov: 31)
  • Exomes 𝑓: 0.57 (176850 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.302

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:):

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-6996310-C-T is Benign according to our data. Variant chr17-6996310-C-T is described in ClinVar as [Benign]. Clinvar id is 1235859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.135+58C>T		intron_variant		ENST00000251535.11	NP_000688.2
ALOX12	XM_011523780.3	c.135+58C>T		intron_variant			XP_011522082.2
ALOX12-AS1	NR_040089.1	n.234-10770G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.135+58C>T		intron_variant		1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89140 AN: 151192 Hom.: 26374 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.574 AC: 613569 AN: 1068026 Hom.: 176850 AF XY: 0.575 AC XY: 289932 AN XY: 504666

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.670

Gnomad4 ASJ exome AF: 0.541

Gnomad4 EAS exome AF: 0.589

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.590 AC: 89213 AN: 151300 Hom.: 26401 Cov.: 31 AF XY: 0.594 AC XY: 43879 AN XY: 73914

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.572

Alfa AF: 0.591 Hom.: 3326

Bravo AF: 0.587

Asia WGS AF: 0.535 AC: 1862 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3218667; hg19: chr17-6899629;