9-38396029-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000692.5(ALDH1B1):c.281G>A(p.Arg94His) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,712 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000025 ( 1 hom. )
Consequence
ALDH1B1
NM_000692.5 missense
NM_000692.5 missense
Scores
1
10
6
Clinical Significance
Conservation
PhyloP100: 6.47
Genes affected
ALDH1B1 (HGNC:407): (aldehyde dehydrogenase 1 family member B1) This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH1B1 | NM_000692.5 | c.281G>A | p.Arg94His | missense_variant | 2/2 | ENST00000377698.4 | |
ALDH1B1 | XM_011517802.3 | c.422G>A | p.Arg141His | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH1B1 | ENST00000377698.4 | c.281G>A | p.Arg94His | missense_variant | 2/2 | 1 | NM_000692.5 | P1 | |
ALDH1B1 | ENST00000635162.1 | c.281G>A | p.Arg94His | missense_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250710Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135550
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461496Hom.: 1 Cov.: 100 AF XY: 0.0000358 AC XY: 26AN XY: 727054
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 07, 2014 | p.Arg94His (CGC>CAC): c.281 G>A in exon 2 of the ALDH1B1 gene (NM_000692.4). The R94H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R94H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Benign
T;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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