rs695214

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000828.5(GRIA3):​c.508+9868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 111,917 control chromosomes in the GnomAD database, including 173 homozygotes. There are 1,851 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 0.054 ( 173 hom., 1851 hem., cov: 24)

Consequence

GRIA3
NM_000828.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0920
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIA3NM_000828.5 linkuse as main transcriptc.508+9868G>A intron_variant ENST00000622768.5
GRIA3NM_007325.5 linkuse as main transcriptc.508+9868G>A intron_variant ENST00000620443.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIA3ENST00000620443.2 linkuse as main transcriptc.508+9868G>A intron_variant 1 NM_007325.5 P4P42263-2
GRIA3ENST00000622768.5 linkuse as main transcriptc.508+9868G>A intron_variant 5 NM_000828.5 A1P42263-1
GRIA3ENST00000620581.4 linkuse as main transcriptc.508+9868G>A intron_variant, NMD_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0544
AC:
6086
AN:
111866
Hom.:
173
Cov.:
24
AF XY:
0.0544
AC XY:
1855
AN XY:
34092
show subpopulations
Gnomad AFR
AF:
0.00937
Gnomad AMI
AF:
0.228
Gnomad AMR
AF:
0.0359
Gnomad ASJ
AF:
0.0855
Gnomad EAS
AF:
0.000281
Gnomad SAS
AF:
0.0128
Gnomad FIN
AF:
0.144
Gnomad MID
AF:
0.0667
Gnomad NFE
AF:
0.0760
Gnomad OTH
AF:
0.0518
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0543
AC:
6081
AN:
111917
Hom.:
173
Cov.:
24
AF XY:
0.0542
AC XY:
1851
AN XY:
34153
show subpopulations
Gnomad4 AFR
AF:
0.00932
Gnomad4 AMR
AF:
0.0359
Gnomad4 ASJ
AF:
0.0855
Gnomad4 EAS
AF:
0.000282
Gnomad4 SAS
AF:
0.0120
Gnomad4 FIN
AF:
0.144
Gnomad4 NFE
AF:
0.0760
Gnomad4 OTH
AF:
0.0512
Alfa
AF:
0.0708
Hom.:
3460
Bravo
AF:
0.0457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
9.8
DANN
Benign
0.82

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.

Other links and lift over

dbSNP: rs695214; hg19: chrX-122397261; API