rs11601239

Variant names:

• chr11-105685872-C-G
• rs11601239
• NM_000829.4:c.248-67109C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-105685872-C-G
• chr11-105685872-C-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.248-67109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,508 control chromosomes in the GnomAD database, including 18,128 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 0.48 (18128 hom., cov: 30)
• Consequence: GRIA4 NM_000829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• Publications: 11 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 = 0.574 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.248-67109C>G		intron	N/A	NP_000820.4
	GRIA4	NM_001440382.1		c.248-67109C>G		intron	N/A	NP_001427311.1
	GRIA4	NM_001440383.1		c.248-67109C>G		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.248-67109C>G		intron	N/A	ENSP00000282499.5
	GRIA4	ENST00000530497.1	TSL:1	c.248-67109C>G		intron	N/A	ENSP00000435775.1
	GRIA4	ENST00000525187.6	TSL:1	c.248-67109C>G		intron	N/A	ENSP00000432180.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72734 AN: 151390 Hom.: 18124 Cov.: 30

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.480 AC: 72755 AN: 151508 Hom.: 18128 Cov.: 30 AF XY: 0.486 AC XY: 35932 AN XY: 73976

African (AFR) AF: 0.335 AC: 13820 AN: 41238

American (AMR) AF: 0.584 AC: 8872 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1841 AN: 3462

East Asian (EAS) AF: 0.385 AC: 1975 AN: 5134

South Asian (SAS) AF: 0.463 AC: 2228 AN: 4808

European-Finnish (FIN) AF: 0.594 AC: 6220 AN: 10464

Middle Eastern (MID) AF: 0.503 AC: 146 AN: 290

European-Non Finnish (NFE) AF: 0.534 AC: 36238 AN: 67904

Other (OTH) AF: 0.480 AC: 1008 AN: 2102

Alfa AF: 0.377 Hom.: 1103

Bravo AF: 0.478

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.36
PhyloP100		-0.55
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: rs11601239; hg19: chr11-105556598;