rs509512

Positions:

• chr11-105974196-C-A
• chr11-105974196-C-G
• chr11-105974196-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.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

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]

LOC124902743 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.2410-114C>A		intron_variant		ENST00000282499.10	NP_000820.4
LOC124902743	XR_007062873.1	n.431+62G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.2410-114C>A		intron_variant		5	NM_000829.4	ENSP00000282499	A1

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

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.668

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.574

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

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.585

Alfa AF: 0.547 Hom.: 9282

Bravo AF: 0.584

Asia WGS AF: 0.599 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.66

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: rs509512; hg19: chr11-105844923;