Variant 17-6999441-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000697.3(ALOX12):c.782A>G(p.Gln261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,612,702 control chromosomes in the GnomAD database, including 276,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 28848 hom., cov: 32)

Exomes 𝑓: 0.58 ( 247954 hom. )

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.59

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:

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

ALOX12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.380869E-6).

BP6

Variant 17-6999441-A-G is Benign according to our data. Variant chr17-6999441-A-G is described in ClinVar as [Benign]. Clinvar id is 1224614.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALOX12	NM_000697.3 linkuse as main transcript	c.782A>G	p.Gln261Arg	missense_variant	6/14	ENST00000251535.11
ALOX12-AS1	NR_040089.1 linkuse as main transcript	n.233+10355T>C		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3 linkuse as main transcript	c.575A>G	p.Gln192Arg	missense_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11 linkuse as main transcript	c.782A>G	p.Gln261Arg	missense_variant	6/14	1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1 linkuse as main transcript	n.139+12755T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93234

AN:

151892

Hom.:

28809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.599

AC:

150620

AN:

251250

Hom.:

45707

AF XY:

0.592

AC XY:

80363

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.699

Gnomad ASJ exome

AF:

0.549

Gnomad EAS exome

AF:

0.510

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.581

AC:

848652

AN:

1460692

Hom.:

247954

Cov.:

AF XY:

0.579

AC XY:

421119

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.664

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.546

Gnomad4 EAS exome

AF:

0.568

Gnomad4 SAS exome

AF:

0.547

Gnomad4 FIN exome

AF:

0.663

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.614

AC:

93323

AN:

152010

Hom.:

28848

Cov.:

AF XY:

0.617

AC XY:

45842

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.663

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.655

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.582

Hom.:

61980

Bravo

AF:

0.615

TwinsUK

AF:

0.573

AC:

2123

ALSPAC

AF:

0.575

AC:

2217

ESP6500AA

AF:

0.667

AC:

2939

ESP6500EA

AF:

0.578

AC:

4970

ExAC

AF:

0.594

AC:

72163

Asia WGS

AF:

0.543

AC:

1894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

This variant is associated with the following publications: (PMID: 20626912, 21104233, 24282679, 16514435, 17460548, 19885615, 22864639, 22977504, 18640486) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0030

DANN

Benign

0.80

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0000034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.19

Sift

Benign

0.23

T;.

Sift4G

Benign

0.71

T;T

Polyphen

0.0

B;.

Vest4

0.0070

MPC

0.30

ClinPred

0.011

GERP RS

-6.1

Varity_R

0.058

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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