17-6996310-C-T

Variant names:

• chr17-6996310-C-T
• rs3218667
• NM_000697.3:c.135+58C>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.135+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,219,326 control chromosomes in the GnomAD database, including 203,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26401 hom., cov: 31)
  • Exomes 𝑓: 0.57 (176850 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.302
• Publications: 3 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=-0.78).
• BP6: Variant 17-6996310-C-T is Benign according to our data. Variant chr17-6996310-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.648 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.135+58C>T		intron	N/A	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-10770G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.135+58C>T		intron	N/A	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.135+58C>T		intron	N/A	ENSP00000585654.1
	MIR497HG	ENST00000399541.7	TSL:2	n.250-10770G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89140 AN: 151192 Hom.: 26374 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.574 AC: 613569 AN: 1068026 Hom.: 176850 AF XY: 0.575 AC XY: 289932 AN XY: 504666

African (AFR) AF: 0.574 AC: 12791 AN: 22280

American (AMR) AF: 0.670 AC: 5339 AN: 7972

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 7378 AN: 13630

East Asian (EAS) AF: 0.589 AC: 14909 AN: 25318

South Asian (SAS) AF: 0.547 AC: 10620 AN: 19420

European-Finnish (FIN) AF: 0.662 AC: 14989 AN: 22638

Middle Eastern (MID) AF: 0.552 AC: 1576 AN: 2856

European-Non Finnish (NFE) AF: 0.573 AC: 522069 AN: 911356

Other (OTH) AF: 0.562 AC: 23898 AN: 42556

GnomAD4 genome AF: 0.590 AC: 89213 AN: 151300 Hom.: 26401 Cov.: 31 AF XY: 0.594 AC XY: 43879 AN XY: 73914

African (AFR) AF: 0.579 AC: 23868 AN: 41242

American (AMR) AF: 0.659 AC: 10046 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2610 AN: 5032

South Asian (SAS) AF: 0.538 AC: 2585 AN: 4802

European-Finnish (FIN) AF: 0.657 AC: 6905 AN: 10502

Middle Eastern (MID) AF: 0.566 AC: 162 AN: 286

European-Non Finnish (NFE) AF: 0.582 AC: 39411 AN: 67714

Other (OTH) AF: 0.572 AC: 1207 AN: 2110

Alfa AF: 0.591 Hom.: 3326

Bravo AF: 0.587

Asia WGS AF: 0.535 AC: 1862 AN: 3470

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	-0.78
CADD	Benign	8.3
DANN	Benign	0.81
PhyloP100		-0.30
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3218667; hg19: chr17-6899629;