5-126575440-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001182.5(ALDH7A1):c.675C>T(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,613,094 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001182.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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ALDH7A1 | NM_001182.5 | c.675C>T | p.Leu225Leu | synonymous_variant | Exon 7 of 18 | ENST00000409134.8 | NP_001173.2 | |
ALDH7A1 | NM_001201377.2 | c.591C>T | p.Leu197Leu | synonymous_variant | Exon 7 of 18 | NP_001188306.1 | ||
ALDH7A1 | NM_001202404.2 | c.675C>T | p.Leu225Leu | synonymous_variant | Exon 7 of 16 | NP_001189333.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0184 AC: 2791AN: 152026Hom.: 83 Cov.: 32
GnomAD3 exomes AF: 0.0121 AC: 3028AN: 250542Hom.: 83 AF XY: 0.0120 AC XY: 1618AN XY: 135380
GnomAD4 exome AF: 0.00491 AC: 7177AN: 1460950Hom.: 184 Cov.: 30 AF XY: 0.00541 AC XY: 3929AN XY: 726724
GnomAD4 genome AF: 0.0184 AC: 2795AN: 152144Hom.: 84 Cov.: 32 AF XY: 0.0178 AC XY: 1322AN XY: 74400
ClinVar
Submissions by phenotype
not specified Benign:5
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
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Pyridoxine-dependent epilepsy Benign:3
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Inborn genetic diseases Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at