Variant 5-153490969-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000827.4(GRIA1):c.81C>A(p.Ile27=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,613,820 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0058 ( 59 hom. )

Consequence

GRIA1
NM_000827.4 splice_region, synonymous

Scores

Splicing: ADA: 0.003172

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.49

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 5-153490969-C-A is Benign according to our data. Variant chr5-153490969-C-A is described in ClinVar as [Benign]. Clinvar id is 717700.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.49 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA1	NM_000827.4 linkuse as main transcript	c.81C>A	p.Ile27=	splice_region_variant, synonymous_variant	1/16	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.81C>A	p.Ile27=	splice_region_variant, synonymous_variant	1/16	1	NM_000827.4	ENSP00000285900	P3	P42261-1

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

988

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00762

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00661

AC:

1661

AN:

251206

Hom.:

AF XY:

0.00658

AC XY:

893

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.00646

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00575

AC:

8408

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4230

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00926

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0298

Gnomad4 NFE exome

AF:

0.00549

Gnomad4 OTH exome

AF:

0.00465

GnomAD4 genome

AF:

0.00649

AC:

988

AN:

152212

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

568

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0367

Gnomad4 NFE

AF:

0.00762

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00612

Hom.:

Bravo

AF:

0.00345

EpiCase

AF:

0.00649

EpiControl

AF:

0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0032

dbscSNV1_RF

Benign

0.16

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