rs2307214

Variant names:

• chr17-7006519-A-G
• rs2307214
• NM_000697.3:c.1452A>G
• ALOX12 p.Gln484Gln

Your query was ambiguous. Multiple possible variants found:

• chr17-7006519-A-G
• chr17-7006519-A-C

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.1452A>G​(p.Gln484Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,613,512 control chromosomes in the GnomAD database, including 8,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (866 hom., cov: 31)
  • Exomes 𝑓: 0.080 (7678 hom.)
• Consequence: ALOX12 NM_000697.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.756
• Publications: 14 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=-0.89).
• BP6: Variant 17-7006519-A-G is Benign according to our data. Variant chr17-7006519-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.756 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	NM_000697.3	MANE Select	c.1452A>G	p.Gln484Gln	synonymous	Exon 11 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.233+3277T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.1452A>G	p.Gln484Gln	synonymous	Exon 11 of 14	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.1638A>G	p.Gln546Gln	synonymous	Exon 11 of 14	ENSP00000585654.1
	MIR497HG	ENST00000399540.3	TSL:2	n.248+3277T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12054 AN: 151982 Hom.: 863 Cov.: 31

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0718

GnomAD2 exomes AF: 0.117 AC: 29443 AN: 250980 AF XY: 0.104

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.0430

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.0991

GnomAD4 exome AF: 0.0797 AC: 116421 AN: 1461412 Hom.: 7678 Cov.: 32 AF XY: 0.0771 AC XY: 56041 AN XY: 727002

African (AFR) AF: 0.0119 AC: 400 AN: 33474

American (AMR) AF: 0.390 AC: 17382 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 1172 AN: 26110

East Asian (EAS) AF: 0.114 AC: 4520 AN: 39684

South Asian (SAS) AF: 0.0357 AC: 3079 AN: 86254

European-Finnish (FIN) AF: 0.137 AC: 7329 AN: 53304

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5760

European-Non Finnish (NFE) AF: 0.0703 AC: 78130 AN: 1111824

Other (OTH) AF: 0.0715 AC: 4318 AN: 60376

GnomAD4 genome AF: 0.0793 AC: 12061 AN: 152100 Hom.: 866 Cov.: 31 AF XY: 0.0858 AC XY: 6374 AN XY: 74332

African (AFR) AF: 0.0170 AC: 706 AN: 41544

American (AMR) AF: 0.246 AC: 3751 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3470

East Asian (EAS) AF: 0.113 AC: 582 AN: 5152

South Asian (SAS) AF: 0.0399 AC: 192 AN: 4812

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10576

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4788 AN: 67966

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0695 Hom.: 948

Bravo AF: 0.0888

Asia WGS AF: 0.0690 AC: 238 AN: 3478

EpiCase AF: 0.0642

EpiControl AF: 0.0604

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		-0.76
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2307214;

hg19: chr17-6909838;

COSMIC: COSV52349664;

COSMIC: COSV52349664;