NM_000829.4:c.2294+8143G>A

Variant names:

• chr11-105942112-G-A
• rs641574
• NM_000829.4:c.2294+8143G>A

Variant summary

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

The NM_000829.4(GRIA4):​c.2294+8143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,742 control chromosomes in the GnomAD database, including 30,278 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 0.63 (30278 hom., cov: 31)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 4 publications found

Genes affected

GRIA4 (HGNC:4574): (glutamate ionotropic receptor AMPA type subunit 4) 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 composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. Some haplotypes of this gene show a positive association with schizophrenia. [provided by RefSeq, Jul 2008]

GRIA4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with or without seizures and gait abnormalities

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.2294+8143G>A		intron_variant	Intron 14 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.2294+8143G>A		intron_variant	Intron 14 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95625 AN: 151626 Hom.: 30263 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.631 AC: 95688 AN: 151742 Hom.: 30278 Cov.: 31 AF XY: 0.627 AC XY: 46510 AN XY: 74134

African (AFR) AF: 0.682 AC: 28255 AN: 41412

American (AMR) AF: 0.562 AC: 8551 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2296 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3240 AN: 5152

South Asian (SAS) AF: 0.674 AC: 3247 AN: 4814

European-Finnish (FIN) AF: 0.595 AC: 6261 AN: 10518

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41782 AN: 67842

Other (OTH) AF: 0.620 AC: 1307 AN: 2108

Alfa AF: 0.620 Hom.: 82694

Bravo AF: 0.632

Asia WGS AF: 0.664 AC: 2306 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.29
PhyloP100		0.0050
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: rs641574; hg19: chr11-105812839;