rs12658202

chr5-153599994-C-Achr5-153599994-C-Gchr5-153599994-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.221-46934C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,802 control chromosomes in the GnomAD database, including 17,303 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 0.46 (17303 hom., cov: 30)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA1	NM_000827.4	c.221-46934C>A		intron_variant		ENST00000285900.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA1	ENST00000285900.10	c.221-46934C>A		intron_variant		1	NM_000827.4	P3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70525 AN: 151684 Hom.: 17299 Cov.: 30

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.465 AC: 70551 AN: 151802 Hom.: 17303 Cov.: 30 AF XY: 0.463 AC XY: 34328 AN XY: 74176

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.450

Alfa AF: 0.521 Hom.: 35394

Bravo AF: 0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.062
Dann	Benign	0.63

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: rs12658202; hg19: chr5-152979554;