rs769407
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000817.3(GAD1):c.638+315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,074 control chromosomes in the GnomAD database, including 4,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.22 ( 4072 hom., cov: 32)
Consequence
GAD1
NM_000817.3 intron
NM_000817.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.852
Genes affected
GAD1 (HGNC:4092): (glutamate decarboxylase 1) This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAD1 | NM_000817.3 | c.638+315G>C | intron_variant | ENST00000358196.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAD1 | ENST00000358196.8 | c.638+315G>C | intron_variant | 1 | NM_000817.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.218 AC: 33080AN: 151958Hom.: 4069 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.218 AC: 33106AN: 152074Hom.: 4072 Cov.: 32 AF XY: 0.222 AC XY: 16466AN XY: 74336
GnomAD4 genome
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1096
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3470
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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