rs2227098

chrX-123361111-C-T

Variant summary

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

The NM_000828.5(GRIA3):c.750+6148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 109,420 control chromosomes in the GnomAD database, including 7,319 homozygotes. There are 13,292 hemizygotes in GnomAD. 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 (7319 hom., 13287 hem., cov: 22)
  • Exomes 𝑓: 0.56 (0 hom. 5 hem.)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) 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 at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.750+6148C>T		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.750+6148C>T		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.750+6148C>T		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.750+6148C>T		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.750+6148C>T		intron_variant, NMD_transcript_variant		1
GRIA3	ENST00000477389.1	n.426-132C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 46687 AN: 109362 Hom.: 7317 Cov.: 22 AF XY: 0.419 AC XY: 13272 AN XY: 31706

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.556 AC: 5 AN: 9 Hom.: 0 AF XY: 0.556 AC XY: 5 AN XY: 9

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.714

GnomAD4 genome AF: 0.427 AC: 46701 AN: 109411 Hom.: 7319 Cov.: 22 AF XY: 0.418 AC XY: 13287 AN XY: 31765

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.450

Alfa AF: 0.450 Hom.: 20531

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.64
Dann	Benign	0.34

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: rs2227098; hg19: chrX-122494962;