chr1-18875462-A-G
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003748.4(ALDH4A1):c.1380T>C(p.Asp460Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,613,800 control chromosomes in the GnomAD database, including 423,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_003748.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- hyperprolinemia type 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH4A1 | NM_003748.4 | c.1380T>C | p.Asp460Asp | synonymous_variant | Exon 13 of 15 | ENST00000375341.8 | NP_003739.2 | |
ALDH4A1 | NM_170726.3 | c.1380T>C | p.Asp460Asp | synonymous_variant | Exon 13 of 16 | NP_733844.1 | ||
ALDH4A1 | NM_001319218.2 | c.1227T>C | p.Asp409Asp | synonymous_variant | Exon 12 of 14 | NP_001306147.1 | ||
ALDH4A1 | NM_001161504.2 | c.1200T>C | p.Asp400Asp | synonymous_variant | Exon 13 of 15 | NP_001154976.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDH4A1 | ENST00000375341.8 | c.1380T>C | p.Asp460Asp | synonymous_variant | Exon 13 of 15 | 1 | NM_003748.4 | ENSP00000364490.3 | ||
ALDH4A1 | ENST00000290597.9 | c.1380T>C | p.Asp460Asp | synonymous_variant | Exon 13 of 16 | 1 | ENSP00000290597.5 | |||
ALDH4A1 | ENST00000538839.5 | c.1227T>C | p.Asp409Asp | synonymous_variant | Exon 12 of 14 | 1 | ENSP00000446071.1 | |||
ALDH4A1 | ENST00000538309.5 | c.1200T>C | p.Asp400Asp | synonymous_variant | Exon 13 of 15 | 2 | ENSP00000442988.1 |
Frequencies
GnomAD3 genomes AF: 0.715 AC: 108516AN: 151872Hom.: 38866 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.732 AC: 184101AN: 251454 AF XY: 0.732 show subpopulations
GnomAD4 exome AF: 0.725 AC: 1059164AN: 1461810Hom.: 384429 Cov.: 67 AF XY: 0.725 AC XY: 527322AN XY: 727222 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.715 AC: 108625AN: 151990Hom.: 38916 Cov.: 31 AF XY: 0.716 AC XY: 53175AN XY: 74296 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Hyperprolinemia type 2 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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not specified Benign:2
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at