rs6426813
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003748.4(ALDH4A1):c.941-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,384,948 control chromosomes in the GnomAD database, including 376,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.72 ( 40377 hom., cov: 33)
Exomes 𝑓: 0.74 ( 336115 hom. )
Consequence
ALDH4A1
NM_003748.4 intron
NM_003748.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.839
Genes affected
ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]
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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 (BayesDel_noAF=-0.91).
BP6
?
Variant 1-18877660-G-A is Benign according to our data. Variant chr1-18877660-G-A is described in ClinVar as [Benign]. Clinvar id is 1188873.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH4A1 | NM_003748.4 | c.941-48C>T | intron_variant | ENST00000375341.8 | |||
ALDH4A1 | NM_001161504.2 | c.761-48C>T | intron_variant | ||||
ALDH4A1 | NM_001319218.2 | c.941-48C>T | intron_variant | ||||
ALDH4A1 | NM_170726.3 | c.941-48C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH4A1 | ENST00000375341.8 | c.941-48C>T | intron_variant | 1 | NM_003748.4 | P1 | |||
ALDH4A1 | ENST00000290597.9 | c.941-48C>T | intron_variant | 1 | P1 | ||||
ALDH4A1 | ENST00000538839.5 | c.941-48C>T | intron_variant | 1 | |||||
ALDH4A1 | ENST00000538309.5 | c.761-48C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.724 AC: 110064AN: 151962Hom.: 40352 Cov.: 33
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GnomAD3 exomes AF: 0.770 AC: 165590AN: 215114Hom.: 64530 AF XY: 0.767 AC XY: 91021AN XY: 118632
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GnomAD4 exome AF: 0.735 AC: 906548AN: 1232868Hom.: 336115 Cov.: 25 AF XY: 0.738 AC XY: 457695AN XY: 620536
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GnomAD4 genome ? AF: 0.724 AC: 110145AN: 152080Hom.: 40377 Cov.: 33 AF XY: 0.726 AC XY: 53997AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperprolinemia type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at