Variant rs707176 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_000827.4(GRIA1):c.531T>C(p.Ile177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,532 control chromosomes in the GnomAD database, including 79,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5962 hom., cov: 31)

Exomes 𝑓: 0.31 ( 73229 hom. )

Consequence

GRIA1
NM_000827.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.861

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 5-153650400-T-C is Benign according to our data. Variant chr5-153650400-T-C is described in ClinVar as [Benign]. Clinvar id is 3059187.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.861 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA1	NM_000827.4 linkuse as main transcript	c.531T>C	p.Ile177=	synonymous_variant	4/16	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10 linkuse as main transcript	c.531T>C	p.Ile177=	synonymous_variant	4/16	1	NM_000827.4	ENSP00000285900	P3	P42261-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39500

AN:

151944

Hom.:

5962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.260

AC:

65161

AN:

250988

Hom.:

9852

AF XY:

0.260

AC XY:

35240

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.0305

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.307

AC:

448063

AN:

1461468

Hom.:

73229

Cov.:

AF XY:

0.302

AC XY:

219935

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.260

AC:

39507

AN:

152064

Hom.:

5962

Cov.:

AF XY:

0.254

AC XY:

18894

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.339

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.318

Hom.:

10328

Bravo

AF:

0.253

Asia WGS

AF:

0.0900

AC:

316

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.333

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRIA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 29, 2023

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.8

DANN

Benign

0.83

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over