Variant 11-105898257-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000829.4(GRIA4):c.727-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 1,388,728 control chromosomes in the GnomAD database, including 6,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.095 ( 849 hom., cov: 32)

Exomes 𝑓: 0.089 ( 5796 hom. )

Consequence

GRIA4
NM_000829.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003433

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.261

Variant links:

Genes affected

GRIA4 (HGNC:4574): (glutamate ionotropic receptor AMPA type subunit 4) 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 of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. Some haplotypes of this gene show a positive association with schizophrenia. [provided by RefSeq, Jul 2008]

GRIA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA4	NM_000829.4 linkuse as main transcript	c.727-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000282499.10	NP_000820.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10 linkuse as main transcript	c.727-12T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000829.4	ENSP00000282499	A1	P48058-1

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14401

AN:

151994

Hom.:

847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.0619

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0819

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.110

AC:

25242

AN:

229484

Hom.:

1862

AF XY:

0.103

AC XY:

12923

AN XY:

124976

show subpopulations

Gnomad AFR exome

AF:

0.0655

Gnomad AMR exome

AF:

0.246

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.0601

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0819

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.0892

AC:

110362

AN:

1236616

Hom.:

5796

Cov.:

AF XY:

0.0878

AC XY:

54869

AN XY:

624666

show subpopulations

Gnomad4 AFR exome

AF:

0.0610

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.0603

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.0818

Gnomad4 OTH exome

AF:

0.0956

GnomAD4 genome

AF:

0.0949

AC:

14428

AN:

152112

Hom.:

849

Cov.:

AF XY:

0.0966

AC XY:

7183

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.0611

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0819

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0911

Hom.:

168

Bravo

AF:

0.103

Asia WGS

AF:

0.100

AC:

345

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

DANN

Benign

0.56

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over