17-6997064-T-C

Variant names:

• chr17-6997064-T-C
• rs312468
• NM_000697.3:c.337+37T>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.337+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,509,778 control chromosomes in the GnomAD database, including 741,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70184 hom., cov: 33)
  • Exomes 𝑓: 0.99 (671085 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• Publications: 7 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=-0.84).
• BP6: Variant 17-6997064-T-C is Benign according to our data. Variant chr17-6997064-T-C is described in ClinVar as Benign. ClinVar VariationId is 1224924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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.337+37T>C		intron	N/A	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-11524A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.337+37T>C		intron	N/A	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.337+37T>C		intron	N/A	ENSP00000585654.1
	ALOX12	ENST00000480801.1	TSL:3	c.46+37T>C		intron	N/A	ENSP00000467033.1	K7ENN9

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145855 AN: 152134 Hom.: 70145 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD2 exomes AF: 0.979 AC: 128207 AN: 130982 AF XY: 0.984

Gnomad AFR exome AF: 0.871

Gnomad AMR exome AF: 0.933

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.995

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.983

GnomAD4 exome AF: 0.994 AC: 1349442 AN: 1357526 Hom.: 671085 Cov.: 62 AF XY: 0.995 AC XY: 660793 AN XY: 664262

African (AFR) AF: 0.868 AC: 26956 AN: 31064

American (AMR) AF: 0.931 AC: 32159 AN: 34530

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23992 AN: 23994

East Asian (EAS) AF: 0.995 AC: 34869 AN: 35040

South Asian (SAS) AF: 0.997 AC: 76602 AN: 76848

European-Finnish (FIN) AF: 1.00 AC: 36944 AN: 36946

Middle Eastern (MID) AF: 0.992 AC: 4194 AN: 4228

European-Non Finnish (NFE) AF: 1.00 AC: 1058079 AN: 1058492

Other (OTH) AF: 0.987 AC: 55647 AN: 56384

GnomAD4 genome AF: 0.959 AC: 145953 AN: 152252 Hom.: 70184 Cov.: 33 AF XY: 0.960 AC XY: 71445 AN XY: 74460

African (AFR) AF: 0.873 AC: 36256 AN: 41512

American (AMR) AF: 0.942 AC: 14411 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5138 AN: 5170

South Asian (SAS) AF: 0.996 AC: 4805 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67997 AN: 68034

Other (OTH) AF: 0.965 AC: 2042 AN: 2116

Alfa AF: 0.973 Hom.: 14266

Bravo AF: 0.948

Asia WGS AF: 0.973 AC: 3385 AN: 3478

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	-0.84
CADD	Benign	0.28
DANN	Benign	0.61
PhyloP100		-1.2
PromoterAI		-0.051	Neutral
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: rs312468; hg19: chr17-6900383;