chr2-170818551-C-CCT
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_000817.3(GAD1):c.-41_-40insCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,578,956 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0021 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0027 ( 7 hom. )
Consequence
GAD1
NM_000817.3 5_prime_UTR
NM_000817.3 5_prime_UTR
Scores
Not classified
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 Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0021 (320/152296) while in subpopulation NFE AF= 0.0035 (238/68028). AF 95% confidence interval is 0.00313. There are 1 homozygotes in gnomad4. There are 162 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAD1 | NM_000817.3 | c.-41_-40insCT | 5_prime_UTR_variant | 2/17 | ENST00000358196.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAD1 | ENST00000358196.8 | c.-41_-40insCT | 5_prime_UTR_variant | 2/17 | 1 | NM_000817.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00210 AC: 320AN: 152178Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.00250 AC: 628AN: 250954Hom.: 1 AF XY: 0.00225 AC XY: 305AN XY: 135734
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GnomAD4 exome AF: 0.00269 AC: 3841AN: 1426660Hom.: 7 Cov.: 26 AF XY: 0.00267 AC XY: 1902AN XY: 712072
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GnomAD4 genome AF: 0.00210 AC: 320AN: 152296Hom.: 1 Cov.: 31 AF XY: 0.00218 AC XY: 162AN XY: 74466
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebral palsy spastic quadriplegic Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at