Genetic Variant ALOX12B:c.-329G>A (chr17-8087771-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001139.3(ALOX12B):c.-329G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 472,870 control chromosomes in the GnomAD database, including 8,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2059 hom., cov: 32)

Exomes 𝑓: 0.19 ( 5984 hom. )

Consequence

ALOX12B
NM_001139.3 upstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.121

Publications

3 publications found

Variant links:

Genes affected

ALOX12B (HGNC:430): (arachidonate 12-lipoxygenase, 12R type) This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

ALOX12B Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital non-bullous ichthyosiform erythroderma
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
self-healing collodion baby
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ALOX12B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12B	NM_001139.3 link	c.-329G>A		upstream_gene_variant		ENST00000647874.1	NP_001130.1	O75342

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1 link	c.-329G>A		upstream_gene_variant			NM_001139.3	ENSP00000497784.1		O75342

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23380

AN:

151948

Hom.:

2053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0733

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.188

AC:

60224

AN:

320804

Hom.:

5984

AF XY:

0.191

AC XY:

31878

AN XY:

166854

show subpopulations

African (AFR)

AF:

0.0733

AC:

756

AN:

10314

American (AMR)

AF:

0.190

AC:

2774

AN:

14592

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

1136

AN:

10764

East Asian (EAS)

AF:

0.165

AC:

3564

AN:

21620

South Asian (SAS)

AF:

0.234

AC:

9627

AN:

41084

European-Finnish (FIN)

AF:

0.184

AC:

2657

AN:

14414

Middle Eastern (MID)

AF:

0.131

AC:

177

AN:

1352

European-Non Finnish (NFE)

AF:

0.193

AC:

36265

AN:

187778

Other (OTH)

AF:

0.173

AC:

3268

AN:

18886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2383

4766

7150

9533

11916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.154

AC:

23408

AN:

152066

Hom.:

2059

Cov.:

AF XY:

0.156

AC XY:

11558

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0735

AC:

3049

AN:

41492

American (AMR)

AF:

0.191

AC:

2922

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3468

East Asian (EAS)

AF:

0.147

AC:

761

AN:

5174

South Asian (SAS)

AF:

0.221

AC:

1068

AN:

4826

European-Finnish (FIN)

AF:

0.176

AC:

1859

AN:

10576

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12891

AN:

67942

Other (OTH)

AF:

0.156

AC:

329

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1006

2012

3018

4024

5030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0850

Hom.:

194

Bravo

AF:

0.150

Asia WGS

AF:

0.176

AC:

614

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

- -

Jun 18, 2021

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

-0.27

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.12

PromoterAI

-0.050

Neutral

(source)

Splicing

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

Publications

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17-8087771-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over