Variant rs2285127 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007325.5(GRIA3):c.268+16606T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000878 in 1,152,103 control chromosomes in the GnomAD database, including 3 homozygotes. There are 465 hemizygotes in GnomAD. 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 0.00059 ( 0 hom., 18 hem., cov: 23)

Exomes 𝑓: 0.00091 ( 3 hom. 447 hem. )

Consequence

GRIA3
NM_007325.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) 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 at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

GRIA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS2

High Hemizygotes in GnomAd4 at 18 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.268+16606T>A	intron_variant	ENST00000622768.5	NP_000819.4	P42263-1Q17R51
GRIA3	NM_007325.5 link	c.268+16606T>A	intron_variant	ENST00000620443.2	NP_015564.5	P42263-2Q17R51
GRIA3	NM_001256743.2 link	c.269-40T>A	intron_variant		NP_001243672.1	Q5XKG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2 link	c.268+16606T>A		intron_variant		1	NM_007325.5	ENSP00000478489.1		P42263-2
GRIA3	ENST00000622768.5 link	c.268+16606T>A		intron_variant		5	NM_000828.5	ENSP00000481554.1		P42263-1

Frequencies

GnomAD3 genomes

AF:

0.000577

AC:

AN:

110968

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

33190

show subpopulations

Gnomad AFR

AF:

0.0000658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

Gnomad ASJ

AF:

0.000379

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00713

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0129

Gnomad NFE

AF:

0.000680

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00166

AC:

169

AN:

101601

Hom.:

AF XY:

0.00234

AC XY:

AN XY:

33397

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000216

Gnomad ASJ exome

AF:

0.000363

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.000909

AC:

946

AN:

1041084

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

447

AN XY:

334128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000405

Gnomad4 AMR exome

AF:

0.000362

Gnomad4 ASJ exome

AF:

0.000491

Gnomad4 EAS exome

AF:

0.000296

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0000273

Gnomad4 NFE exome

AF:

0.000381

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.000585

AC:

AN:

111019

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

AN XY:

33251

show subpopulations

Gnomad4 AFR

AF:

0.0000657

Gnomad4 AMR

AF:

0.0000951

Gnomad4 ASJ

AF:

0.000379

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00752

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000680

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.000490

Hom.:

3944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.21

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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