rs472792

Variant names:

• chr5-153491624-C-A
• rs472792
• NM_000827.4:c.82+654C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-153491624-C-A
• chr5-153491624-C-G
• chr5-153491624-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000827.4(GRIA1):​c.82+654C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,730 control chromosomes in the GnomAD database, including 46,242 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 0.77 (46242 hom., cov: 30)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.82+654C>A		intron_variant	Intron 1 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.82+654C>A		intron_variant	Intron 1 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117371 AN: 151612 Hom.: 46173 Cov.: 30

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.774 AC: 117501 AN: 151730 Hom.: 46242 Cov.: 30 AF XY: 0.773 AC XY: 57312 AN XY: 74120

African (AFR) AF: 0.920 AC: 38071 AN: 41360

American (AMR) AF: 0.819 AC: 12498 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4406 AN: 5132

South Asian (SAS) AF: 0.691 AC: 3314 AN: 4798

European-Finnish (FIN) AF: 0.683 AC: 7195 AN: 10536

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47267 AN: 67856

Other (OTH) AF: 0.765 AC: 1616 AN: 2112

Alfa AF: 0.719 Hom.: 17405

Bravo AF: 0.795

Asia WGS AF: 0.793 AC: 2755 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.060
PromoterAI		0.013	Neutral
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: rs472792; hg19: chr5-152871184; COSMIC: COSV53622757; COSMIC: COSV53622757;