rs13138842

Positions:

• chr4-157221940-A-G
• chr4-157221940-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001083619.3(GRIA2):​c.229+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 769,922 control chromosomes in the GnomAD database, including 254,992 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 0.80 (48483 hom., cov: 29)
  • Exomes 𝑓: 0.82 (206509 hom.)
• Consequence: GRIA2 NM_001083619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA2	NM_001083619.3	c.229+133A>G		intron_variant		ENST00000264426.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA2	ENST00000264426.14	c.229+133A>G		intron_variant		1	NM_001083619.3	P4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121062 AN: 151668 Hom.: 48458 Cov.: 29

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.816 AC: 504462 AN: 618132 Hom.: 206509 AF XY: 0.817 AC XY: 265470 AN XY: 324866

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.823

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.844

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.806

GnomAD4 genome AF: 0.798 AC: 121133 AN: 151790 Hom.: 48483 Cov.: 29 AF XY: 0.799 AC XY: 59225 AN XY: 74142

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.794

Alfa AF: 0.785 Hom.: 6192

Bravo AF: 0.798

Asia WGS AF: 0.810 AC: 2815 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs13138842; hg19: chr4-158143092;