dbSNP rs312466: ALOX12-AS1:n.234-10362C>T (chr17-6995902-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000399541.6(ALOX12-AS1):n.234-10362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,158 control chromosomes in the GnomAD database, including 9,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9632 hom., cov: 34)

Consequence

ALOX12-AS1
ENST00000399541.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.773

Variant links:

Genes affected

ALOX12-AS1 (HGNC:):

ALOX12-AS1 links:

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

ALOX12-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-6995902-G-A is Benign according to our data. Variant chr17-6995902-G-A is described in ClinVar as [Benign]. Clinvar id is 1178415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALOX12-AS1	NR_040089.1 link	n.234-10362C>T	intron_variant	Intron 2 of 2
ALOX12	NM_000697.3 link	c.-216G>A	upstream_gene_variant		ENST00000251535.11	NP_000688.2	P18054
ALOX12	XM_011523780.3 link	c.-216G>A	upstream_gene_variant			XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 link	c.-216G>A		upstream_gene_variant		1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51616

AN:

152040

Hom.:

9624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.367

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

GnomAD4 genome

AF:

0.339

AC:

51626

AN:

152158

Hom.:

9632

Cov.:

AF XY:

0.337

AC XY:

25113

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.418

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.397

Hom.:

10752

Bravo

AF:

0.327

Asia WGS

AF:

0.426

AC:

1478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.8

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over