NM_000827.4:c.2271-3807G>A

Variant names:

• chr5-153790814-G-A
• rs4958351
• NM_000827.4:c.2271-3807G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000827.4(GRIA1):​c.2271-3807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,766 control chromosomes in the GnomAD database, including 7,489 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 0.30 (7489 hom., cov: 31)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 24 publications found

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]

GRIA1 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 67

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual developmental disorder, autosomal recessive 76

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.2271-3807G>A		intron_variant	Intron 13 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.2271-3807G>A		intron_variant	Intron 13 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46269 AN: 151648 Hom.: 7491 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.305 AC: 46264 AN: 151766 Hom.: 7489 Cov.: 31 AF XY: 0.302 AC XY: 22358 AN XY: 74112

African (AFR) AF: 0.259 AC: 10716 AN: 41354

American (AMR) AF: 0.233 AC: 3553 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3466

East Asian (EAS) AF: 0.0320 AC: 165 AN: 5154

South Asian (SAS) AF: 0.411 AC: 1975 AN: 4810

European-Finnish (FIN) AF: 0.337 AC: 3525 AN: 10466

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23830 AN: 67948

Other (OTH) AF: 0.322 AC: 679 AN: 2106

Alfa AF: 0.329 Hom.: 3329

Bravo AF: 0.291

Asia WGS AF: 0.222 AC: 772 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	0.53
DANN	Benign	0.59
PhyloP100		0.0070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4958351; hg19: chr5-153170374;