11-105898257-T-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000829.4(GRIA4):c.727-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 1,388,728 control chromosomes in the GnomAD database, including 6,645 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 0.095 ( 849 hom., cov: 32)
Exomes 𝑓: 0.089 ( 5796 hom. )
Consequence
GRIA4
NM_000829.4 splice_polypyrimidine_tract, intron
NM_000829.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003433
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.261
Genes affected
GRIA4 (HGNC:4574): (glutamate ionotropic receptor AMPA type subunit 4) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. Some haplotypes of this gene show a positive association with schizophrenia. [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=-0.84).
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA4 | NM_000829.4 | c.727-12T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000282499.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA4 | ENST00000282499.10 | c.727-12T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000829.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0947 AC: 14401AN: 151994Hom.: 847 Cov.: 32
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GnomAD3 exomes AF: 0.110 AC: 25242AN: 229484Hom.: 1862 AF XY: 0.103 AC XY: 12923AN XY: 124976
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GnomAD4 exome AF: 0.0892 AC: 110362AN: 1236616Hom.: 5796 Cov.: 17 AF XY: 0.0878 AC XY: 54869AN XY: 624666
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GnomAD4 genome ? AF: 0.0949 AC: 14428AN: 152112Hom.: 849 Cov.: 32 AF XY: 0.0966 AC XY: 7183AN XY: 74388
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at