11-105942112-G-A

Position:

• chr11-105942112-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.2294+8143G>A		intron_variant		ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.2294+8143G>A		intron_variant		5	NM_000829.4	ENSP00000282499	A1

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

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.620

Alfa AF: 0.616 Hom.: 53773

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs641574; hg19: chr11-105812839;