chr4-157364445-T-G

Variant names:

• chr4-157364445-T-G
• rs4403097
• NM_001083619.3:c.*1014T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083619.3(GRIA2):​c.*1014T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: GRIA2 NM_001083619.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 10 publications found

Genes affected

GRIA2 (HGNC:4572): (glutamate ionotropic receptor AMPA type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [provided by RefSeq, Jul 2008]

GRIA2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language impairment and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA2	NM_001083619.3	MANE Select	c.*1014T>G		3_prime_UTR	Exon 16 of 16	NP_001077088.2
	GRIA2	NM_000826.6		c.*1014T>G		3_prime_UTR	Exon 16 of 16	NP_000817.5
	GRIA2	NM_001083620.3		c.*1014T>G		3_prime_UTR	Exon 16 of 16	NP_001077089.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA2	ENST00000264426.14	TSL:1 MANE Select	c.*1014T>G		3_prime_UTR	Exon 16 of 16	ENSP00000264426.9
	GRIA2	ENST00000296526.12	TSL:1	c.*1014T>G		3_prime_UTR	Exon 16 of 16	ENSP00000296526.7
	GRIA2	ENST00000393815.6	TSL:1	c.*1014T>G		3_prime_UTR	Exon 16 of 16	ENSP00000377403.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		1.2

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: rs4403097; hg19: chr4-158285597;