rs72842957

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

1
5
12

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]

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
ALOX12BNM_001139.3 linkuse as main transcriptc.379C>T p.Pro127Ser missense_variant 3/15 ENST00000647874.1 NP_001130.1
LOC107985075XR_001752778.2 linkuse as main transcriptn.1434G>A non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALOX12BENST00000647874.1 linkuse as main transcriptc.379C>T p.Pro127Ser missense_variant 3/15 NM_001139.3 ENSP00000497784 P1
ENST00000399413.3 linkuse as main transcriptn.1400G>A non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.0150
AC:
2277
AN:
152070
Hom.:
38
Cov.:
31
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.:
84
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.:
33
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.:
38
Cov.:
31
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.:
80
Bravo
AF:
0.0158
TwinsUK
AF:
0.0210
AC:
78
ALSPAC
AF:
0.0153
AC:
59
ESP6500AA
AF:
0.00409
AC:
18
ESP6500EA
AF:
0.0227
AC:
195
ExAC
AF:
0.0171
AC:
2080
Asia WGS
AF:
0.00549
AC:
20
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 17, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This variant is associated with the following publications: (PMID: 27884173, 16116617, 20981092, 17139268, 22995991) -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2024ALOX12B: BP4, BS1, BS2; ENSG00000214999: BS1, BS2 -
not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpFeb 17, 2022- -
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This 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
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D;D
Eigen
Benign
-0.095
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.77
.;T
MetaRNN
Benign
0.0052
T;T
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
0.51
D
PrimateAI
Benign
0.41
T
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
T
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.

Other links and lift over

dbSNP: rs72842957; hg19: chr17-7984479; COSMIC: COSV99063550; COSMIC: COSV99063550; API