rs6503075

Variant names:

• chr17-8075433-G-A
• rs6503075
• NM_001139.3:c.1654+162C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001139.3(ALOX12B):​c.1654+162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,966 control chromosomes in the GnomAD database, including 17,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (17289 hom., cov: 32)
• Consequence: ALOX12B NM_001139.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570
• Publications: 5 publications found

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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-8075433-G-A is Benign according to our data. Variant chr17-8075433-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12B	NM_001139.3	MANE Select	c.1654+162C>T		intron	N/A	NP_001130.1	O75342

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12B	ENST00000647874.1	MANE Select	c.1654+162C>T		intron	N/A	ENSP00000497784.1	O75342
	ALOX12B	ENST00000649809.1		c.718+162C>T		intron	N/A	ENSP00000496845.1	A0A3B3IRK2
	ALOX12B	ENST00000577351.5	TSL:5	n.479+742C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72265 AN: 151848 Hom.: 17282 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.476 AC: 72307 AN: 151966 Hom.: 17289 Cov.: 32 AF XY: 0.474 AC XY: 35204 AN XY: 74288

African (AFR) AF: 0.483 AC: 19999 AN: 41432

American (AMR) AF: 0.411 AC: 6283 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5164

South Asian (SAS) AF: 0.557 AC: 2684 AN: 4822

European-Finnish (FIN) AF: 0.438 AC: 4626 AN: 10562

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33864 AN: 67926

Other (OTH) AF: 0.457 AC: 964 AN: 2108

Alfa AF: 0.494 Hom.: 10918

Bravo AF: 0.470

Asia WGS AF: 0.397 AC: 1386 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		0.057
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6503075; hg19: chr17-7978751; COSMIC: COSV59874436; COSMIC: COSV59874436;