11-105826169-T-C

Variant names:

• chr11-105826169-T-C
• rs610160
• NM_000829.4:c.488-35855T>C

Variant summary

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

The NM_000829.4(GRIA4):​c.488-35855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,866 control chromosomes in the GnomAD database, including 2,603 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 0.17 (2603 hom., cov: 32)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.488-35855T>C		intron_variant	Intron 4 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.488-35855T>C		intron_variant	Intron 4 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25875 AN: 151748 Hom.: 2591 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.171 AC: 25926 AN: 151866 Hom.: 2603 Cov.: 32 AF XY: 0.169 AC XY: 12567 AN XY: 74210

African (AFR) AF: 0.268 AC: 11076 AN: 41402

American (AMR) AF: 0.236 AC: 3588 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3466

East Asian (EAS) AF: 0.166 AC: 854 AN: 5146

South Asian (SAS) AF: 0.0945 AC: 455 AN: 4814

European-Finnish (FIN) AF: 0.0885 AC: 937 AN: 10582

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7941 AN: 67918

Other (OTH) AF: 0.170 AC: 358 AN: 2102

Alfa AF: 0.156 Hom.: 419

Bravo AF: 0.191

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.58
PhyloP100		-0.21
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: rs610160; hg19: chr11-105696895;