rs2508467

Variant names:

• chr11-105887378-G-A
• rs2508467
• NM_000829.4:c.673-141G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-105887378-G-A
• chr11-105887378-G-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.673-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 485,796 control chromosomes in the GnomAD database, including 13,826 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 0.25 (4882 hom., cov: 32)
  • Exomes 𝑓: 0.23 (8944 hom.)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.673-141G>A		intron_variant	Intron 5 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.673-141G>A		intron_variant	Intron 5 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38053 AN: 151694 Hom.: 4866 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.227 AC: 75701 AN: 333986 Hom.: 8944 AF XY: 0.223 AC XY: 39454 AN XY: 177210

African (AFR) AF: 0.256 AC: 2048 AN: 7998

American (AMR) AF: 0.295 AC: 2632 AN: 8926

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 2669 AN: 10574

East Asian (EAS) AF: 0.147 AC: 3417 AN: 23310

South Asian (SAS) AF: 0.139 AC: 3265 AN: 23456

European-Finnish (FIN) AF: 0.251 AC: 7701 AN: 30726

Middle Eastern (MID) AF: 0.194 AC: 299 AN: 1542

European-Non Finnish (NFE) AF: 0.236 AC: 48902 AN: 207524

Other (OTH) AF: 0.239 AC: 4768 AN: 19930

GnomAD4 genome AF: 0.251 AC: 38101 AN: 151810 Hom.: 4882 Cov.: 32 AF XY: 0.249 AC XY: 18499 AN XY: 74196

African (AFR) AF: 0.270 AC: 11187 AN: 41424

American (AMR) AF: 0.291 AC: 4436 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 921 AN: 3466

East Asian (EAS) AF: 0.195 AC: 1005 AN: 5166

South Asian (SAS) AF: 0.145 AC: 701 AN: 4818

European-Finnish (FIN) AF: 0.253 AC: 2656 AN: 10500

Middle Eastern (MID) AF: 0.192 AC: 55 AN: 286

European-Non Finnish (NFE) AF: 0.242 AC: 16438 AN: 67860

Other (OTH) AF: 0.269 AC: 568 AN: 2110

Alfa AF: 0.208 Hom.: 1083

Bravo AF: 0.255

Asia WGS AF: 0.183 AC: 634 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.27
PhyloP100		0.86
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: rs2508467; hg19: chr11-105758104;