rs11542313
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000817.3(GAD1):āc.111T>Cā(p.His37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,610,348 control chromosomes in the GnomAD database, including 136,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.35 ( 10293 hom., cov: 32)
Exomes š: 0.41 ( 126414 hom. )
Consequence
GAD1
NM_000817.3 synonymous
NM_000817.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.140
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 2-170822115-T-C is Benign according to our data. Variant chr2-170822115-T-C is described in ClinVar as [Benign]. Clinvar id is 332226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-170822115-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.14 with no splicing effect.
BA1
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GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAD1 | NM_000817.3 | c.111T>C | p.His37= | synonymous_variant | 3/17 | ENST00000358196.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAD1 | ENST00000358196.8 | c.111T>C | p.His37= | synonymous_variant | 3/17 | 1 | NM_000817.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.354 AC: 53787AN: 151902Hom.: 10295 Cov.: 32
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GnomAD3 exomes AF: 0.394 AC: 96714AN: 245232Hom.: 19618 AF XY: 0.401 AC XY: 53102AN XY: 132532
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GnomAD4 exome AF: 0.414 AC: 603037AN: 1458330Hom.: 126414 Cov.: 41 AF XY: 0.414 AC XY: 300001AN XY: 725066
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GnomAD4 genome ? AF: 0.354 AC: 53789AN: 152018Hom.: 10293 Cov.: 32 AF XY: 0.355 AC XY: 26406AN XY: 74300
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Developmental and epileptic encephalopathy 89 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
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BayesDel_noAF
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CADD
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DANN
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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