rs11601239

chr11-105685872-C-Gchr11-105685872-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000829.4(GRIA4):c.248-67109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,508 control chromosomes in the GnomAD database, including 18,128 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 0.48 (18128 hom., cov: 30)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA4	NM_000829.4	c.248-67109C>G		intron_variant		ENST00000282499.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA4	ENST00000282499.10	c.248-67109C>G		intron_variant		5	NM_000829.4	A1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72734 AN: 151390 Hom.: 18124 Cov.: 30

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.480 AC: 72755 AN: 151508 Hom.: 18128 Cov.: 30 AF XY: 0.486 AC XY: 35932 AN XY: 73976

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.480

Alfa AF: 0.377 Hom.: 1103

Bravo AF: 0.478

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.16
Dann	Benign	0.36

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: rs11601239; hg19: chr11-105556598;