17-6998976-G-A

Position:

chr17-6998976-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000251535.11(ALOX12):c.566G>A(p.Arg189His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,096 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 9 hom. )

Consequence

ALOX12
ENST00000251535.11 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.27

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:):

ALOX12-AS1 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 (MetaRNN=0.0055149198).

BP6

Variant 17-6998976-G-A is Benign according to our data. Variant chr17-6998976-G-A is described in ClinVar as [Benign]. Clinvar id is 791340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (984/152226) while in subpopulation AFR AF= 0.0224 (929/41534). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12	NM_000697.3 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	5/14	ENST00000251535.11	NP_000688.2	P18054
ALOX12	XM_011523780.3 linkuse as main transcript	c.542+139G>A		intron_variant			XP_011522082.2
ALOX12-AS1	NR_040089.1 linkuse as main transcript	n.233+10820C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	5/14	1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

AF:

0.00648

AC:

986

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00179

AC:

449

AN:

251466

Hom.:

AF XY:

0.00130

AC XY:

177

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000639

AC:

934

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

386

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00646

AC:

984

AN:

152226

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

469

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00750

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00212

AC:

257

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.97

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

REVEL

Benign

0.27

Sift

Benign

0.14

Sift4G

Benign

0.24

Polyphen

0.97

Vest4

0.11

MVP

0.87

MPC

0.36

ClinPred

0.029

GERP RS

4.0

Varity_R

0.090

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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