Genetic Variant NM_000827.4:c.82+1259dupC (chr5-153492228-T-TC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000827.4(GRIA1):c.82+1259dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,535,256 control chromosomes in the GnomAD database, including 3,243 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.086 ( 1195 hom., cov: 31)

Exomes 𝑓: 0.030 ( 2048 hom. )

Consequence

GRIA1
NM_000827.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.645

Variant links:

Genes affected

GRIA1 (HGNC:4571): (glutamate ionotropic receptor AMPA type subunit 1) 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 with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GRIA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-153492228-T-TC is Benign according to our data. Variant chr5-153492228-T-TC is described in ClinVar as [Benign]. Clinvar id is 218567.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4 link	c.82+1259dupC		intron_variant	Intron 1 of 15	ENST00000285900.10	NP_000818.2	P42261-1Q59GL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10 link	c.82+1259dupC		intron_variant	Intron 1 of 15	1	NM_000827.4	ENSP00000285900.4		P42261-1

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13069

AN:

152080

Hom.:

1189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0371

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.0436

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0490

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0757

GnomAD3 exomes

AF:

0.0502

AC:

6434

AN:

128232

Hom.:

408

AF XY:

0.0533

AC XY:

3744

AN XY:

70202

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0495

Gnomad EAS exome

AF:

0.0397

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.0406

Gnomad NFE exome

AF:

0.0167

Gnomad OTH exome

AF:

0.0356

GnomAD4 exome

AF:

0.0305

AC:

42139

AN:

1383058

Hom.:

2048

Cov.:

AF XY:

0.0325

AC XY:

22152

AN XY:

682426

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0468

Gnomad4 EAS exome

AF:

0.0763

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0410

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0407

GnomAD4 genome

AF:

0.0861

AC:

13097

AN:

152198

Hom.:

1195

Cov.:

AF XY:

0.0870

AC XY:

6472

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.0426

Gnomad4 EAS

AF:

0.0439

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0490

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0744

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0912

Asia WGS

AF:

0.0880

AC:

304

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GRIA1-related disorder

Benign:1

Nov 29, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over