rs1994862

Positions:

• chr5-153609350-C-G
• chr5-153609350-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.221-37578C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,904 control chromosomes in the GnomAD database, including 4,487 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 0.23 (4487 hom., cov: 31)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.221-37578C>G		intron_variant		ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.221-37578C>G		intron_variant		1	NM_000827.4	ENSP00000285900	P3

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35031 AN: 151786 Hom.: 4480 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.231 AC: 35071 AN: 151904 Hom.: 4487 Cov.: 31 AF XY: 0.227 AC XY: 16875 AN XY: 74234

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00291

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.227

Alfa AF: 0.162 Hom.: 347

Bravo AF: 0.216

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.46

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: rs1994862; hg19: chr5-152988910;