rs3749033
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1
The NM_000817.3(GAD1):c.639-1156T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 600,982 control chromosomes in the GnomAD database, including 20,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.21 ( 3987 hom., cov: 32)
Exomes 𝑓: 0.26 ( 16729 hom. )
Consequence
GAD1
NM_000817.3 intron
NM_000817.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.24
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=-0.43).
BP6
?
Variant 2-170842889-T-A is Benign according to our data. Variant chr2-170842889-T-A is described in ClinVar as [Benign]. Clinvar id is 1269663.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAD1 | NM_000817.3 | c.639-1156T>A | intron_variant | ENST00000358196.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAD1 | ENST00000358196.8 | c.639-1156T>A | intron_variant | 1 | NM_000817.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.212 AC: 32215AN: 152032Hom.: 3986 Cov.: 32
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GnomAD4 exome AF: 0.264 AC: 118715AN: 448832Hom.: 16729 AF XY: 0.270 AC XY: 63237AN XY: 234056
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GnomAD4 genome ? AF: 0.212 AC: 32226AN: 152150Hom.: 3987 Cov.: 32 AF XY: 0.216 AC XY: 16059AN XY: 74384
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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