rs10041275

chr5-153682601-T-Cchr5-153682601-T-G

Variant summary

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

The NM_000827.4(GRIA1):c.1030-3624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,908 control chromosomes in the GnomAD database, including 8,890 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 0.32 (8890 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA1	NM_000827.4	c.1030-3624T>C		intron_variant		ENST00000285900.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA1	ENST00000285900.10	c.1030-3624T>C		intron_variant		1	NM_000827.4	P3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49277 AN: 151790 Hom.: 8888 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.325 AC: 49303 AN: 151908 Hom.: 8890 Cov.: 32 AF XY: 0.325 AC XY: 24132 AN XY: 74204

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.339

Alfa AF: 0.258 Hom.: 7236

Bravo AF: 0.332

Asia WGS AF: 0.447 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.86

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: rs10041275; hg19: chr5-153062161;