11-105974196-C-A

Variant names:

• chr11-105974196-C-A
• rs509512
• NM_000829.4:c.2410-114C>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.2410-114C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 990,342 control chromosomes in the GnomAD database, including 162,823 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 0.57 (24665 hom., cov: 32)
  • Exomes 𝑓: 0.57 (138158 hom.)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• 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: G2P, ClinGen, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

LOC124902743 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000829.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA4	NM_000829.4	MANE Select	c.2410-114C>A		intron	N/A	NP_000820.4	P48058-1
	GRIA4	NM_001440382.1		c.2410-114C>A		intron	N/A	NP_001427311.1
	GRIA4	NM_001440383.1		c.2410-114C>A		intron	N/A	NP_001427312.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA4	ENST00000282499.10	TSL:5 MANE Select	c.2410-114C>A		intron	N/A	ENSP00000282499.5	P48058-1
	GRIA4	ENST00000530497.1	TSL:1	c.2410-114C>A		intron	N/A	ENSP00000435775.1	P48058-1
	GRIA4	ENST00000525187.6	TSL:1	c.2410-114C>A		intron	N/A	ENSP00000432180.1	G3V164

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86514 AN: 151952 Hom.: 24653 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.572 AC: 479147 AN: 838272 Hom.: 138158 AF XY: 0.572 AC XY: 246707 AN XY: 430964

African (AFR) AF: 0.570 AC: 11660 AN: 20454

American (AMR) AF: 0.668 AC: 19961 AN: 29886

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 10163 AN: 17084

East Asian (EAS) AF: 0.620 AC: 22644 AN: 36530

South Asian (SAS) AF: 0.616 AC: 36513 AN: 59320

European-Finnish (FIN) AF: 0.489 AC: 22935 AN: 46860

Middle Eastern (MID) AF: 0.661 AC: 2825 AN: 4274

European-Non Finnish (NFE) AF: 0.564 AC: 330143 AN: 584978

Other (OTH) AF: 0.574 AC: 22303 AN: 38886

GnomAD4 genome AF: 0.569 AC: 86559 AN: 152070 Hom.: 24665 Cov.: 32 AF XY: 0.566 AC XY: 42083 AN XY: 74342

African (AFR) AF: 0.573 AC: 23751 AN: 41456

American (AMR) AF: 0.616 AC: 9418 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2047 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3093 AN: 5184

South Asian (SAS) AF: 0.620 AC: 2993 AN: 4826

European-Finnish (FIN) AF: 0.491 AC: 5193 AN: 10572

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38143 AN: 67970

Other (OTH) AF: 0.585 AC: 1235 AN: 2112

Alfa AF: 0.549 Hom.: 10609

Bravo AF: 0.584

Asia WGS AF: 0.599 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		0.038
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: rs509512; hg19: chr11-105844923;