rs2073438

chr17-6996757-G-A

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.136-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,517,478 control chromosomes in the GnomAD database, including 56,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3917 hom., cov: 33)
  • Exomes 𝑓: 0.27 (52789 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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=-0.89).
• BP6: Variant 17-6996757-G-A is Benign according to our data. Variant chr17-6996757-G-A is described in ClinVar as [Benign]. Clinvar id is 1220801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.136-69G>A		intron_variant		ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.234-11217C>T		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.136-69G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.136-69G>A		intron_variant		1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+15439C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30966 AN: 152060 Hom.: 3914 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.271 AC: 369898 AN: 1365300 Hom.: 52789 AF XY: 0.268 AC XY: 179123 AN XY: 668940

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.203 AC: 30967 AN: 152178 Hom.: 3917 Cov.: 33 AF XY: 0.202 AC XY: 15032 AN XY: 74398

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.221

Alfa AF: 0.264 Hom.: 6762

Bravo AF: 0.192

Asia WGS AF: 0.224 AC: 776 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	-0.89
Cadd	Benign	0.67
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2073438; hg19: chr17-6900076; COSMIC: COSV52350070; COSMIC: COSV52350070;