rs2195450

chr5-153491449-G-A

Variant summary

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

The NM_000827.4(GRIA1):c.82+479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 320,324 control chromosomes in the GnomAD database, including 7,915 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 0.17 (2870 hom., cov: 31)
  • Exomes 𝑓: 0.24 (5045 hom.)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA1	NM_000827.4	c.82+479G>A		intron_variant		ENST00000285900.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA1	ENST00000285900.10	c.82+479G>A		intron_variant		1	NM_000827.4	P3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26218 AN: 151912 Hom.: 2870 Cov.: 31

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.242 AC: 40657 AN: 168294 Hom.: 5045 AF XY: 0.240 AC XY: 19509 AN XY: 81262

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0943

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.172 AC: 26218 AN: 152030 Hom.: 2870 Cov.: 31 AF XY: 0.169 AC XY: 12538 AN XY: 74292

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.181

Alfa AF: 0.208 Hom.: 455

Bravo AF: 0.168

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	12
Dann	Benign	0.91

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: rs2195450; hg19: chr5-152871009;