11-105978187-C-T

Variant names:

• chr11-105978187-C-T
• rs659840
• NM_000829.4:c.2545-1388C>T

Variant summary

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

The NM_000829.4(GRIA4):​c.2545-1388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,794 control chromosomes in the GnomAD database, including 31,728 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 0.65 (31728 hom., cov: 32)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 1 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

LOC124902743 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.2545-1388C>T		intron_variant	Intron 16 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.2545-1388C>T		intron_variant	Intron 16 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98024 AN: 151676 Hom.: 31713 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.646 AC: 98083 AN: 151794 Hom.: 31728 Cov.: 32 AF XY: 0.642 AC XY: 47635 AN XY: 74184

African (AFR) AF: 0.674 AC: 27929 AN: 41430

American (AMR) AF: 0.670 AC: 10222 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3470

East Asian (EAS) AF: 0.626 AC: 3233 AN: 5162

South Asian (SAS) AF: 0.679 AC: 3274 AN: 4824

European-Finnish (FIN) AF: 0.570 AC: 6019 AN: 10552

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42880 AN: 67790

Other (OTH) AF: 0.660 AC: 1393 AN: 2110

Alfa AF: 0.630 Hom.: 3893

Bravo AF: 0.660

Asia WGS AF: 0.665 AC: 2295 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		-1.5
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: rs659840; hg19: chr11-105848914;