chr11-105611002-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000829.4(GRIA4):c.5G>A(p.Arg2Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
GRIA4
NM_000829.4 missense
NM_000829.4 missense
Scores
1
4
11
Clinical Significance
Conservation
PhyloP100: 7.25
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 Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GRIA4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36345112).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIA4 | NM_000829.4 | c.5G>A | p.Arg2Lys | missense_variant | 2/17 | ENST00000282499.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIA4 | ENST00000282499.10 | c.5G>A | p.Arg2Lys | missense_variant | 2/17 | 5 | NM_000829.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151578Hom.: 0 Cov.: 29
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251390Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1457606Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725438
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151690Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 74108
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2023 | The c.5G>A (p.R2K) alteration is located in exon 2 (coding exon 1) of the GRIA4 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the arginine (R) at amino acid position 2 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;T;D;D;T;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.083, 0.14
.;.;.;B;B;.;.;.;.;B;B
Vest4
0.69, 0.69, 0.65, 0.60, 0.61, 0.57, 0.61
MutPred
Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);Gain of methylation at R2 (P = 0.0718);
MVP
MPC
0.27
ClinPred
T
GERP RS
Varity_R
gMVP
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