Genetic Variant NM_001083619.3:c.2043+1162G>A (chr4-157342624-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001083619.3(GRIA2):c.2043+1162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 186,854 control chromosomes in the GnomAD database, including 4,277 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 0.19 ( 4111 hom., cov: 32)

Exomes 𝑓: 0.080 ( 166 hom. )

Consequence

GRIA2
NM_001083619.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA2	NM_001083619.3 link	c.2043+1162G>A		intron_variant	Intron 12 of 15	ENST00000264426.14	NP_001077088.2	P42262-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA2	ENST00000264426.14 link	c.2043+1162G>A		intron_variant	Intron 12 of 15	1	NM_001083619.3	ENSP00000264426.9		P42262-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28109

AN:

151690

Hom.:

4098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.0885

Gnomad FIN

AF:

0.0801

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0901

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.0797

AC:

2794

AN:

35046

Hom.:

166

AF XY:

0.0781

AC XY:

1334

AN XY:

17086

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.0682

Gnomad4 ASJ exome

AF:

0.0333

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.0559

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0743

Gnomad4 OTH exome

AF:

0.0832

GnomAD4 genome

AF:

0.185

AC:

28148

AN:

151808

Hom.:

4111

Cov.:

AF XY:

0.181

AC XY:

13462

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.0883

Gnomad4 FIN

AF:

0.0801

Gnomad4 NFE

AF:

0.0901

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.0760

Hom.:

159

Bravo

AF:

0.200

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.54

DANN

Benign

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over