chr17-8081161-G-A

Position:

chr17-8081161-G-A

Variant summary

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

The NM_001139.3(ALOX12B):c.379C>T(p.Pro127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,613,950 control chromosomes in the GnomAD database, including 384 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 38 hom., cov: 31)

Exomes 𝑓: 0.019 ( 346 hom. )

Consequence

ALOX12B
NM_001139.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.60

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 links:

(HGNC:):

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=0.0051826537).

BP6

Variant 17-8081161-G-A is Benign according to our data. Variant chr17-8081161-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 402365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8081161-G-A is described in Lovd as [Benign]. Variant chr17-8081161-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.015 (2278/152188) while in subpopulation AMR AF= 0.0201 (308/15300). AF 95% confidence interval is 0.0183. There are 38 homozygotes in gnomad4. There are 1086 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	NM_001139.3 linkuse as main transcript	c.379C>T	p.Pro127Ser	missense_variant	3/15	ENST00000647874.1	NP_001130.1
LOC107985075	XR_001752778.2 linkuse as main transcript	n.1434G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1 linkuse as main transcript	c.379C>T	p.Pro127Ser	missense_variant	3/15		NM_001139.3	ENSP00000497784	P1
	ENST00000399413.3 linkuse as main transcript	n.1400G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2277

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0907

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0176

AC:

4418

AN:

251072

Hom.:

AF XY:

0.0181

AC XY:

2455

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0835

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0188

AC:

27467

AN:

1461762

Hom.:

346

Cov.:

AF XY:

0.0189

AC XY:

13725

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.0842

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0185

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0150

AC:

2278

AN:

152188

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1086

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.0907

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0206

Hom.:

Bravo

AF:

0.0158

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0227

AC:

195

ExAC

AF:

0.0171

AC:

2080

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0218

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 17, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 27884173, 16116617, 20981092, 17139268, 22995991) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ALOX12B: BP4, BS1, BS2; ENSG00000214999: BS1, BS2 -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 17, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 2.2% (1456/66124) European -

Autosomal recessive congenital ichthyosis 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;D

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0052

T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.51

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.7

D;.

REVEL

Uncertain

0.33

Sift

Benign

0.10

T;.

Sift4G

Uncertain

0.035

D;.

Polyphen

0.62

P;P

Vest4

0.046

MPC

0.70

ClinPred

0.040

GERP RS

4.1

Varity_R

0.22

gMVP

0.46

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

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