17-6998976-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000697.3(ALOX12):c.566G>A(p.Arg189His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,096 control chromosomes in the GnomAD database, including 20 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 Benign (★).
Frequency
Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00064 ( 9 hom. )
Consequence
ALOX12
NM_000697.3 missense
NM_000697.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
ALOX12 (HGNC:429): (arachidonate 12-lipoxygenase, 12S type) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0055149198).
BP6
?
Variant 17-6998976-G-A is Benign according to our data. Variant chr17-6998976-G-A is described in ClinVar as [Benign]. Clinvar id is 791340.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (984/152226) while in subpopulation AFR AF= 0.0224 (929/41534). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALOX12 | NM_000697.3 | c.566G>A | p.Arg189His | missense_variant | 5/14 | ENST00000251535.11 | |
ALOX12-AS1 | NR_040089.1 | n.233+10820C>T | intron_variant, non_coding_transcript_variant | ||||
ALOX12 | XM_011523780.3 | c.542+139G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALOX12 | ENST00000251535.11 | c.566G>A | p.Arg189His | missense_variant | 5/14 | 1 | NM_000697.3 | P1 | |
ALOX12-AS1 | ENST00000653385.1 | n.139+13220C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00648 AC: 986AN: 152108Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00179 AC: 449AN: 251466Hom.: 4 AF XY: 0.00130 AC XY: 177AN XY: 135902
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GnomAD4 exome AF: 0.000639 AC: 934AN: 1461870Hom.: 9 Cov.: 36 AF XY: 0.000531 AC XY: 386AN XY: 727240
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GnomAD4 genome ? AF: 0.00646 AC: 984AN: 152226Hom.: 11 Cov.: 32 AF XY: 0.00630 AC XY: 469AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at