rs113539426

Variant names:

• chr17-8111545-G-A
• rs113539426
• NM_021628.3:c.785-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8111545-G-A
• chr17-8111545-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021628.3(ALOXE3):​c.785-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,613,964 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (67 hom., cov: 32)
  • Exomes 𝑓: 0.026 (639 hom.)
• Consequence: ALOXE3 NM_021628.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

Genes affected

ALOXE3 (HGNC:13743): (arachidonate lipoxygenase 3) This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ALOXE3 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-8111545-G-A is Benign according to our data. Variant chr17-8111545-G-A is described in ClinVar as Benign. ClinVar VariationId is 261425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOXE3	NM_021628.3	c.785-14C>T		intron_variant	Intron 7 of 15	ENST00000448843.7	NP_067641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOXE3	ENST00000448843.7	c.785-14C>T		intron_variant	Intron 7 of 15	1	NM_021628.3	ENSP00000400581.2

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3493 AN: 152224 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0238 AC: 5991 AN: 251248 AF XY: 0.0242

Gnomad AFR exome AF: 0.00450

Gnomad AMR exome AF: 0.0189

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0313

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0258 AC: 37673 AN: 1461622 Hom.: 639 Cov.: 32 AF XY: 0.0258 AC XY: 18760 AN XY: 727126

African (AFR) AF: 0.00574 AC: 192 AN: 33476

American (AMR) AF: 0.0206 AC: 920 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0656 AC: 1714 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0129 AC: 1116 AN: 86240

European-Finnish (FIN) AF: 0.0298 AC: 1589 AN: 53392

Middle Eastern (MID) AF: 0.101 AC: 577 AN: 5708

European-Non Finnish (NFE) AF: 0.0268 AC: 29749 AN: 1111862

Other (OTH) AF: 0.0300 AC: 1814 AN: 60388

GnomAD4 genome AF: 0.0229 AC: 3488 AN: 152342 Hom.: 67 Cov.: 32 AF XY: 0.0229 AC XY: 1709 AN XY: 74494

African (AFR) AF: 0.00591 AC: 246 AN: 41592

American (AMR) AF: 0.0280 AC: 429 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4826

European-Finnish (FIN) AF: 0.0285 AC: 303 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2051 AN: 68032

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0271 Hom.: 123

Bravo AF: 0.0227

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive congenital ichthyosis 3 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.80
CADD	Benign	10
DANN	Benign	0.46
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113539426; hg19: chr17-8014863;