17-6997526-C-T

Position:

• chr17-6997526-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000697.3(ALOX12):​c.337+499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 149,824 control chromosomes in the GnomAD database, including 25,329 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25329 hom., cov: 27)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65

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]

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.337+499C>T		intron_variant		ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.234-11986G>A		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.337+499C>T		intron_variant			XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.337+499C>T		intron_variant		1	NM_000697.3	ENSP00000251535	P1
ALOX12-AS1	ENST00000653385.1	n.139+14670G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.580 AC: 86828 AN: 149720 Hom.: 25309 Cov.: 27

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.555

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.570

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 86892 AN: 149824 Hom.: 25329 Cov.: 27 AF XY: 0.584 AC XY: 42574 AN XY: 72932

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.569

Alfa AF: 0.534 Hom.: 3782

Bravo AF: 0.575

Asia WGS AF: 0.516 AC: 1798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs10852889; hg19: chr17-6900845; COSMIC: COSV52349120; COSMIC: COSV52349120;