rs312470

Variant names:

• chr17-6998860-G-A
• rs312470
• NM_000697.3:c.542+23G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-6998860-G-A
• chr17-6998860-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000697.3(ALOX12):​c.542+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,613,954 control chromosomes in the GnomAD database, including 659,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52833 hom., cov: 31)
  • Exomes 𝑓: 0.91 (606628 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-6998860-G-A is Benign according to our data. Variant chr17-6998860-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.542+23G>A		intron_variant	Intron 4 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.233+10936C>T		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.542+23G>A		intron_variant	Intron 4 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.542+23G>A		intron_variant	Intron 4 of 13	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125256 AN: 152012 Hom.: 52812 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.852

GnomAD2 exomes AF: 0.847 AC: 212795 AN: 251286 AF XY: 0.869

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.941

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.856

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.907 AC: 1325798 AN: 1461824 Hom.: 606628 Cov.: 61 AF XY: 0.911 AC XY: 662537 AN XY: 727218

African (AFR) AF: 0.653 AC: 21862 AN: 33474

American (AMR) AF: 0.530 AC: 23682 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 24542 AN: 26128

East Asian (EAS) AF: 0.881 AC: 34970 AN: 39700

South Asian (SAS) AF: 0.957 AC: 82523 AN: 86258

European-Finnish (FIN) AF: 0.861 AC: 45986 AN: 53420

Middle Eastern (MID) AF: 0.960 AC: 5539 AN: 5768

European-Non Finnish (NFE) AF: 0.928 AC: 1032317 AN: 1111986

Other (OTH) AF: 0.900 AC: 54377 AN: 60392

GnomAD4 genome AF: 0.824 AC: 125322 AN: 152130 Hom.: 52833 Cov.: 31 AF XY: 0.821 AC XY: 61030 AN XY: 74380

African (AFR) AF: 0.670 AC: 27798 AN: 41464

American (AMR) AF: 0.669 AC: 10220 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3242 AN: 3472

East Asian (EAS) AF: 0.879 AC: 4548 AN: 5174

South Asian (SAS) AF: 0.951 AC: 4584 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8987 AN: 10596

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63069 AN: 68006

Other (OTH) AF: 0.853 AC: 1803 AN: 2114

Alfa AF: 0.854 Hom.: 12256

Bravo AF: 0.796

Asia WGS AF: 0.873 AC: 3037 AN: 3478

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

- -

Nov 10, 2018

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	-0.83
CADD	Benign	6.3
DANN	Benign	0.69
PhyloP100		0.035
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: rs312470; hg19: chr17-6902179; COSMIC: COSV52352443; COSMIC: COSV52352443;