rs2508467

Positions:

• chr11-105887378-G-A
• chr11-105887378-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000829.4(GRIA4):​c.673-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 485,796 control chromosomes in the GnomAD database, including 13,826 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 0.25 (4882 hom., cov: 32)
  • Exomes 𝑓: 0.23 (8944 hom.)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857

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]

GRIA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.673-141G>A		intron_variant		ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.673-141G>A		intron_variant		5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38053 AN: 151694 Hom.: 4866 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.227 AC: 75701 AN: 333986 Hom.: 8944 AF XY: 0.223 AC XY: 39454 AN XY: 177210

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.251 AC: 38101 AN: 151810 Hom.: 4882 Cov.: 32 AF XY: 0.249 AC XY: 18499 AN XY: 74196

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.269

Alfa AF: 0.202 Hom.: 935

Bravo AF: 0.255

Asia WGS AF: 0.183 AC: 634 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.27

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: rs2508467; hg19: chr11-105758104;