rs2028816

Positions:

• chr11-105701113-G-A
• chr11-105701113-G-C

Variant summary

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

The NM_000829.4(GRIA4):​c.248-51868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,880 control chromosomes in the GnomAD database, including 17,878 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 0.48 (17878 hom., cov: 32)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.248-51868G>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.248-51868G>A		intron_variant		5	NM_000829.4	ENSP00000282499	A1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72423 AN: 151758 Hom.: 17872 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72450 AN: 151880 Hom.: 17878 Cov.: 32 AF XY: 0.481 AC XY: 35713 AN XY: 74220

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.480

Alfa AF: 0.488 Hom.: 2277

Bravo AF: 0.478

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.69

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: rs2028816; hg19: chr11-105571839;