5-153752746-T-C

Variant names:

• chr5-153752746-T-C
• rs11167640
• NM_000827.4:c.1824-11688T>C

Variant summary

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

The NM_000827.4(GRIA1):​c.1824-11688T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,078 control chromosomes in the GnomAD database, including 6,588 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 0.26 (6588 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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 (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.1824-11688T>C		intron_variant	Intron 11 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.1824-11688T>C		intron_variant	Intron 11 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39593 AN: 151960 Hom.: 6573 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.261 AC: 39639 AN: 152078 Hom.: 6588 Cov.: 32 AF XY: 0.270 AC XY: 20046 AN XY: 74342

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.251

Alfa AF: 0.263 Hom.: 927

Bravo AF: 0.272

Asia WGS AF: 0.559 AC: 1939 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.52

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: rs11167640; hg19: chr5-153132306;