rs312462

Variant names:

• chr17-7010333-G-A
• rs312462
• NM_000697.3:c.1902G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000697.3(ALOX12):​c.1902G>A​(p.Leu634Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,614,104 control chromosomes in the GnomAD database, including 9,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (743 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8930 hom.)
• Consequence: ALOX12 NM_000697.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258
• Publications: 28 publications found

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]

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-7010333-G-A is Benign according to our data. Variant chr17-7010333-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.1902G>A	p.Leu634Leu	synonymous_variant	Exon 14 of 14	ENST00000251535.11	NP_000688.2
ALOX12	XM_011523780.3	c.1695G>A	p.Leu565Leu	synonymous_variant	Exon 13 of 13		XP_011522082.2
ALOX12-AS1	NR_040089.1	n.140-444C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.1902G>A	p.Leu634Leu	synonymous_variant	Exon 14 of 14	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13847 AN: 152122 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.0969

GnomAD2 exomes AF: 0.113 AC: 28395 AN: 251392 AF XY: 0.119

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.0571

Gnomad NFE exome AF: 0.0970

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.104 AC: 152322 AN: 1461864 Hom.: 8930 Cov.: 32 AF XY: 0.108 AC XY: 78580 AN XY: 727232

African (AFR) AF: 0.0671 AC: 2246 AN: 33480

American (AMR) AF: 0.0991 AC: 4434 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3769 AN: 26130

East Asian (EAS) AF: 0.133 AC: 5283 AN: 39700

South Asian (SAS) AF: 0.214 AC: 18499 AN: 86248

European-Finnish (FIN) AF: 0.0592 AC: 3165 AN: 53418

Middle Eastern (MID) AF: 0.142 AC: 818 AN: 5768

European-Non Finnish (NFE) AF: 0.0966 AC: 107439 AN: 1112000

Other (OTH) AF: 0.110 AC: 6669 AN: 60396

GnomAD4 genome AF: 0.0910 AC: 13849 AN: 152240 Hom.: 743 Cov.: 32 AF XY: 0.0919 AC XY: 6841 AN XY: 74442

African (AFR) AF: 0.0655 AC: 2720 AN: 41532

American (AMR) AF: 0.0805 AC: 1232 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.145 AC: 754 AN: 5184

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4828

European-Finnish (FIN) AF: 0.0542 AC: 575 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6589 AN: 68002

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.101 Hom.: 1190

Bravo AF: 0.0905

Asia WGS AF: 0.166 AC: 578 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs312462; hg19: chr17-6913652; COSMIC: COSV52349019; COSMIC: COSV52349019;