5-153497448-C-T

Variant names:

• chr5-153497448-C-T
• rs1428920
• NM_000827.4:c.220+3383C>T

Variant summary

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

The NM_000827.4(GRIA1):​c.220+3383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,970 control chromosomes in the GnomAD database, including 11,323 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 0.37 (11323 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.220+3383C>T		intron_variant	Intron 2 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.220+3383C>T		intron_variant	Intron 2 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56870 AN: 151850 Hom.: 11290 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.375 AC: 56941 AN: 151970 Hom.: 11323 Cov.: 32 AF XY: 0.381 AC XY: 28264 AN XY: 74256

African (AFR) AF: 0.351 AC: 14563 AN: 41434

American (AMR) AF: 0.517 AC: 7898 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3507 AN: 5162

South Asian (SAS) AF: 0.531 AC: 2555 AN: 4810

European-Finnish (FIN) AF: 0.309 AC: 3259 AN: 10552

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22484 AN: 67954

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.355 Hom.: 37226

Bravo AF: 0.390

Asia WGS AF: 0.567 AC: 1967 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.76
PhyloP100		0.34
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: rs1428920; hg19: chr5-152877008;