17-6996412-T-C

Position:

• chr17-6996412-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000697.3(ALOX12):​c.135+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,220 control chromosomes in the GnomAD database, including 70,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.96 (70207 hom., cov: 31)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-6996412-T-C is Benign according to our data. Variant chr17-6996412-T-C is described in ClinVar as [Benign]. Clinvar id is 1182711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.135+160T>C		intron_variant		ENST00000251535.11	NP_000688.2
ALOX12-AS1	NR_040089.1	n.234-10872A>G		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.135+160T>C		intron_variant			XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.135+160T>C		intron_variant		1	NM_000697.3	ENSP00000251535	P1
ALOX12-AS1	ENST00000653385.1	n.139+15784A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145877 AN: 152104 Hom.: 70168 Cov.: 31

Gnomad AFR AF: 0.875

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

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

GnomAD4 genome AF: 0.959 AC: 145974 AN: 152220 Hom.: 70207 Cov.: 31 AF XY: 0.960 AC XY: 71427 AN XY: 74424

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.965

Alfa AF: 0.985 Hom.: 14055

Bravo AF: 0.949

Asia WGS AF: 0.973 AC: 3386 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs167494; hg19: chr17-6899731;