Genetic Variant NM_000697.3:c.338-156G>A (chr17-6998353-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000697.3(ALOX12):c.338-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,010 control chromosomes in the GnomAD database, including 9,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 9266 hom., cov: 31)

Consequence

ALOX12
NM_000697.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0640

Publications

20 publications found

Variant links:

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 links:

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

MIR497HG links:

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

ALOX12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-6998353-G-A is Benign according to our data. Variant chr17-6998353-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277668.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3 link	c.338-156G>A	intron_variant	Intron 2 of 13	ENST00000251535.11	NP_000688.2	P18054
ALOX12-AS1	NR_040089.1 link	n.233+11443C>T	intron_variant	Intron 2 of 2
ALOX12	XM_011523780.3 link	c.338-156G>A	intron_variant	Intron 2 of 12		XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 link	c.338-156G>A		intron_variant	Intron 2 of 13	1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48982

AN:

151892

Hom.:

9265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.360

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

GnomAD4 genome

AF:

0.322

AC:

48986

AN:

152010

Hom.:

9266

Cov.:

AF XY:

0.324

AC XY:

24042

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.113

AC:

4682

AN:

41490

American (AMR)

AF:

0.314

AC:

4801

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1412

AN:

3470

East Asian (EAS)

AF:

0.403

AC:

2077

AN:

5160

South Asian (SAS)

AF:

0.356

AC:

1714

AN:

4814

European-Finnish (FIN)

AF:

0.417

AC:

4395

AN:

10546

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28613

AN:

67946

Other (OTH)

AF:

0.361

AC:

761

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1571

3142

4714

6285

7856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.394

Hom.:

52833

Bravo

AF:

0.300

Asia WGS

AF:

0.352

AC:

1223

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.53

PhyloP100

0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over