17-6999140-T-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.646+84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,504,218 control chromosomes in the GnomAD database, including 7,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (880 hom., cov: 32)
  • Exomes 𝑓: 0.079 (6944 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365

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=-0.91).
• BP6: Variant 17-6999140-T-C is Benign according to our data. Variant chr17-6999140-T-C is described in ClinVar as [Benign]. Clinvar id is 1178469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.646+84T>C		intron_variant		ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.233+10656A>G		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.543-269T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.646+84T>C		intron_variant		1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+13056A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12162 AN: 152040 Hom.: 877 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0795 AC: 107482 AN: 1352060 Hom.: 6944 Cov.: 22 AF XY: 0.0770 AC XY: 52080 AN XY: 675968

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.0440

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.0351

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0717

GnomAD4 genome AF: 0.0800 AC: 12169 AN: 152158 Hom.: 880 Cov.: 32 AF XY: 0.0865 AC XY: 6432 AN XY: 74358

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0760 Hom.: 109

Bravo AF: 0.0891

Asia WGS AF: 0.0700 AC: 242 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	-0.91
Cadd	Benign	2.8
Dann	Benign	0.52

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: rs2307215; hg19: chr17-6902459;