rs12189362

chr5-153677988-C-T

Variant summary

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

The NM_000827.4(GRIA1):c.1029+827C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,136 control chromosomes in the GnomAD database, including 1,015 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 0.11 (1015 hom., cov: 33)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

Genes affected

GRIA1 (HGNC:4571): (glutamate ionotropic receptor AMPA type subunit 1) 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 with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA1	NM_000827.4	c.1029+827C>T		intron_variant		ENST00000285900.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA1	ENST00000285900.10	c.1029+827C>T		intron_variant		1	NM_000827.4	P3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16736 AN: 152018 Hom.: 1014 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.110 AC: 16760 AN: 152136 Hom.: 1015 Cov.: 33 AF XY: 0.112 AC XY: 8326 AN XY: 74370

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0676

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.110

Alfa AF: 0.108 Hom.: 1713

Bravo AF: 0.103

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.5
Dann	Benign	0.79

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: rs12189362; hg19: chr5-153057548;