rs4424038

Variant names:

• chr5-153740704-A-G
• rs4424038
• NM_000827.4:c.1824-23730A>G

Variant summary

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

The NM_000827.4(GRIA1):​c.1824-23730A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,030 control chromosomes in the GnomAD database, including 7,153 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 0.28 (7153 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 5 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: ClinGen
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	NM_000827.4	MANE Select	c.1824-23730A>G		intron	N/A	NP_000818.2	P42261-1
	GRIA1	NM_001258021.2		c.1854-23730A>G		intron	N/A	NP_001244950.1	P42261-5
	GRIA1	NM_001258022.2		c.1854-23730A>G		intron	N/A	NP_001244951.1	P42261-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	ENST00000285900.10	TSL:1 MANE Select	c.1824-23730A>G		intron	N/A	ENSP00000285900.4	P42261-1
	GRIA1	ENST00000340592.10	TSL:1	c.1824-23730A>G		intron	N/A	ENSP00000339343.5	P42261-2
	GRIA1	ENST00000706733.1		c.1824-23730A>G		intron	N/A	ENSP00000516520.1	A0A9L9PYA4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41994 AN: 151912 Hom.: 7138 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.277 AC: 42040 AN: 152030 Hom.: 7153 Cov.: 32 AF XY: 0.284 AC XY: 21124 AN XY: 74336

African (AFR) AF: 0.261 AC: 10815 AN: 41466

American (AMR) AF: 0.383 AC: 5843 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 734 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4724 AN: 5160

South Asian (SAS) AF: 0.360 AC: 1733 AN: 4808

European-Finnish (FIN) AF: 0.243 AC: 2568 AN: 10578

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14887 AN: 67956

Other (OTH) AF: 0.266 AC: 562 AN: 2116

Alfa AF: 0.272 Hom.: 1050

Bravo AF: 0.289

Asia WGS AF: 0.564 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		0.20
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: rs4424038; hg19: chr5-153120264;