17-6996240-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000697.3(ALOX12):c.123C>G(p.Pro41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,245,516 control chromosomes in the GnomAD database, including 611,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69848 hom., cov: 33)
  • Exomes 𝑓: 1.0 (541952 hom.)
• Consequence: ALOX12 NM_000697.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.10

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-6996240-C-G is Benign according to our data. Variant chr17-6996240-C-G is described in ClinVar as [Benign]. Clinvar id is 1269497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.
• 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	UniProt
ALOX12	NM_000697.3	c.123C>G	p.Pro41=	synonymous_variant	1/14	ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.234-10700G>C		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.123C>G	p.Pro41=	synonymous_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.123C>G	p.Pro41=	synonymous_variant	1/14	1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+15956G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145456 AN: 152058 Hom.: 69812 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.942

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: 0.960

GnomAD3 exomes AF: 0.997 AC: 8851 AN: 8874 Hom.: 4416 AF XY: 0.998 AC XY: 4412 AN XY: 4422

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.980

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.995 AC: 1088361 AN: 1093350 Hom.: 541952 Cov.: 70 AF XY: 0.996 AC XY: 515261 AN XY: 517398

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.995

Gnomad4 SAS exome AF: 0.996

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.987

GnomAD4 genome AF: 0.956 AC: 145546 AN: 152166 Hom.: 69848 Cov.: 33 AF XY: 0.957 AC XY: 71209 AN XY: 74384

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.941

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: 0.961

Alfa AF: 0.989 Hom.: 3490

Bravo AF: 0.948

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.19
Dann	Benign	0.83

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: rs312467; hg19: chr17-6899559; COSMIC: COSV52348402; COSMIC: COSV52348402;