rs2073438

Variant names:

• chr17-6996757-G-A
• rs2073438
• NM_000697.3:c.136-69G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-6996757-G-A
• chr17-6996757-G-C
• chr17-6996757-G-T

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.93
• Publications: 31 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=-0.89).
• BP6: Variant 17-6996757-G-A is Benign according to our data. Variant chr17-6996757-G-A is described in ClinVar as Benign. ClinVar VariationId is 1220801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.136-69G>A		intron_variant	Intron 1 of 13	ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.234-11217C>T		intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3	c.136-69G>A		intron_variant	Intron 1 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.136-69G>A		intron_variant	Intron 1 of 13	1	NM_000697.3	ENSP00000251535.6

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

African (AFR) AF: 0.0462 AC: 1447 AN: 31314

American (AMR) AF: 0.117 AC: 4015 AN: 34368

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 5890 AN: 21550

East Asian (EAS) AF: 0.298 AC: 11253 AN: 37710

South Asian (SAS) AF: 0.152 AC: 11384 AN: 75126

European-Finnish (FIN) AF: 0.256 AC: 12710 AN: 49586

Middle Eastern (MID) AF: 0.190 AC: 1021 AN: 5378

European-Non Finnish (NFE) AF: 0.292 AC: 307411 AN: 1054144

Other (OTH) AF: 0.263 AC: 14767 AN: 56124

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

African (AFR) AF: 0.0583 AC: 2420 AN: 41538

American (AMR) AF: 0.159 AC: 2430 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1683 AN: 5166

South Asian (SAS) AF: 0.156 AC: 753 AN: 4830

European-Finnish (FIN) AF: 0.266 AC: 2816 AN: 10578

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19209 AN: 67992

Other (OTH) AF: 0.221 AC: 467 AN: 2114

Alfa AF: 0.265 Hom.: 8745

Bravo AF: 0.192

Asia WGS AF: 0.224 AC: 776 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	-0.89
CADD	Benign	0.67
DANN	Benign	0.75
PhyloP100		-1.9
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs2073438; hg19: chr17-6900076; COSMIC: COSV52350070; COSMIC: COSV52350070;