4-157364445-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083619.3(GRIA2):​c.*1014T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,356 control chromosomes in the GnomAD database, including 18,679 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 0.45 (18666 hom., cov: 31)
  • Exomes 𝑓: 0.59 (13 hom.)
• Consequence: GRIA2 NM_001083619.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA2	NM_001083619.3	c.*1014T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000264426.14	NP_001077088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA2	ENST00000264426.14	c.*1014T>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_001083619.3	ENSP00000264426.9

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68238 AN: 151148 Hom.: 18667 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.589 AC: 53 AN: 90 Hom.: 13 Cov.: 0 AF XY: 0.567 AC XY: 34 AN XY: 60

Gnomad4 FIN exome AF: 0.591

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.451 AC: 68241 AN: 151266 Hom.: 18666 Cov.: 31 AF XY: 0.457 AC XY: 33754 AN XY: 73890

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.480

Alfa AF: 0.489 Hom.: 3029

Bravo AF: 0.437

Asia WGS AF: 0.606 AC: 2090 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.64

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: rs4403097; hg19: chr4-158285597;