Variant rs4302506 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001083619.3(GRIA2):c.687T>C(p.His229His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,208,880 control chromosomes in the GnomAD database, including 246,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30113 hom., cov: 32)

Exomes 𝑓: 0.63 ( 215989 hom. )

Consequence

GRIA2
NM_001083619.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.58

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 4-157317678-T-C is Benign according to our data. Variant chr4-157317678-T-C is described in ClinVar as [Benign]. Clinvar id is 1266895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA2	NM_001083619.3 link	c.687T>C	p.His229His	synonymous_variant	5/16	ENST00000264426.14	NP_001077088.2	P42262-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA2	ENST00000264426.14 link	c.687T>C	p.His229His	synonymous_variant	5/16	1	NM_001083619.3	ENSP00000264426.9		P42262-1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94767

AN:

151796

Hom.:

30101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.724

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.647

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.674

AC:

161742

AN:

240144

Hom.:

55418

AF XY:

0.671

AC XY:

87557

AN XY:

130438

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.650

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.633

AC:

669281

AN:

1056966

Hom.:

215989

Cov.:

AF XY:

0.637

AC XY:

345672

AN XY:

542972

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.712

Gnomad4 FIN exome

AF:

0.640

Gnomad4 NFE exome

AF:

0.612

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.624

AC:

94811

AN:

151914

Hom.:

30113

Cov.:

AF XY:

0.627

AC XY:

46563

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.711

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.822

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.647

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.628

Hom.:

13748

Bravo

AF:

0.622

Asia WGS

AF:

0.730

AC:

2530

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.3

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over