rs3813296

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001083619.3(GRIA2):​c.2291+228T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,012 control chromosomes in the GnomAD database, including 16,500 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 0.43 ( 16500 hom., cov: 32)

Consequence

GRIA2
NM_001083619.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597
Variant links:
Genes affected
GRIA2 (HGNC:4572): (glutamate ionotropic receptor AMPA type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [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=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIA2NM_001083619.3 linkuse as main transcriptc.2291+228T>G intron_variant ENST00000264426.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIA2ENST00000264426.14 linkuse as main transcriptc.2291+228T>G intron_variant 1 NM_001083619.3 P4P42262-1

Frequencies

GnomAD3 genomes
AF:
0.428
AC:
64973
AN:
151892
Hom.:
16488
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.723
Gnomad AMI
AF:
0.322
Gnomad AMR
AF:
0.340
Gnomad ASJ
AF:
0.325
Gnomad EAS
AF:
0.308
Gnomad SAS
AF:
0.177
Gnomad FIN
AF:
0.297
Gnomad MID
AF:
0.320
Gnomad NFE
AF:
0.323
Gnomad OTH
AF:
0.412
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.428
AC:
65024
AN:
152012
Hom.:
16500
Cov.:
32
AF XY:
0.421
AC XY:
31242
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.722
Gnomad4 AMR
AF:
0.339
Gnomad4 ASJ
AF:
0.325
Gnomad4 EAS
AF:
0.308
Gnomad4 SAS
AF:
0.177
Gnomad4 FIN
AF:
0.297
Gnomad4 NFE
AF:
0.323
Gnomad4 OTH
AF:
0.413
Alfa
AF:
0.379
Hom.:
1587
Bravo
AF:
0.449
Asia WGS
AF:
0.289
AC:
1000
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
10
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3813296; hg19: chr4-158281523; API