rs17104711

Variant names:

• chr11-105902736-G-A
• rs17104711
• NM_000829.4:c.886-1078G>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.886-1078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,204 control chromosomes in the GnomAD database, including 742 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 0.083 (742 hom., cov: 32)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.886-1078G>A		intron_variant	Intron 7 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.886-1078G>A		intron_variant	Intron 7 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12561 AN: 152086 Hom.: 743 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.0826 AC: 12569 AN: 152204 Hom.: 742 Cov.: 32 AF XY: 0.0846 AC XY: 6298 AN XY: 74402

African (AFR) AF: 0.0273 AC: 1134 AN: 41548

American (AMR) AF: 0.182 AC: 2780 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3468

East Asian (EAS) AF: 0.159 AC: 825 AN: 5178

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0817 AC: 5558 AN: 68000

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.0716 Hom.: 244

Bravo AF: 0.0888

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.57
PhyloP100		-2.2
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: rs17104711; hg19: chr11-105773462;