NM_000829.4:c.247+29900A>T

Variant names:

• chr11-105642334-A-T
• rs3170
• NM_000829.4:c.247+29900A>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.247+29900A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,664 control chromosomes in the GnomAD database, including 8,591 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 0.33 (8591 hom., cov: 30)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4	c.247+29900A>T		intron_variant	Intron 3 of 16	ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10	c.247+29900A>T		intron_variant	Intron 3 of 16	5	NM_000829.4	ENSP00000282499.5

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49292 AN: 151546 Hom.: 8581 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.325 AC: 49347 AN: 151664 Hom.: 8591 Cov.: 30 AF XY: 0.329 AC XY: 24392 AN XY: 74098

African (AFR) AF: 0.401 AC: 16562 AN: 41328

American (AMR) AF: 0.464 AC: 7054 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3464

East Asian (EAS) AF: 0.390 AC: 2003 AN: 5134

South Asian (SAS) AF: 0.368 AC: 1763 AN: 4792

European-Finnish (FIN) AF: 0.265 AC: 2794 AN: 10534

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17264 AN: 67896

Other (OTH) AF: 0.331 AC: 697 AN: 2104

Alfa AF: 0.286 Hom.: 831

Bravo AF: 0.349

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.50
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: rs3170; hg19: chr11-105513061;