dbSNP rs509512: GRIA4:c.2410-114C>A (chr11-105974196-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000829.4(GRIA4):c.2410-114C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 990,342 control chromosomes in the GnomAD database, including 162,823 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.

Frequency

Genomes: 𝑓 0.57 ( 24665 hom., cov: 32)

Exomes 𝑓: 0.57 ( 138158 hom. )

Consequence

GRIA4
NM_000829.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

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:

LOC124902743 (HGNC:):

LOC124902743 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA4	NM_000829.4 link	c.2410-114C>A		intron_variant	Intron 15 of 16	ENST00000282499.10	NP_000820.4	P48058-1Q1WWK6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA4	ENST00000282499.10 link	c.2410-114C>A		intron_variant	Intron 15 of 16	5	NM_000829.4	ENSP00000282499.5		P48058-1

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86514

AN:

151952

Hom.:

24653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.589

GnomAD4 exome

AF:

0.572

AC:

479147

AN:

838272

Hom.:

138158

AF XY:

0.572

AC XY:

246707

AN XY:

430964

show subpopulations

African (AFR)

AF:

0.570

AC:

11660

AN:

20454

American (AMR)

AF:

0.668

AC:

19961

AN:

29886

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

10163

AN:

17084

East Asian (EAS)

AF:

0.620

AC:

22644

AN:

36530

South Asian (SAS)

AF:

0.616

AC:

36513

AN:

59320

European-Finnish (FIN)

AF:

0.489

AC:

22935

AN:

46860

Middle Eastern (MID)

AF:

0.661

AC:

2825

AN:

4274

European-Non Finnish (NFE)

AF:

0.564

AC:

330143

AN:

584978

Other (OTH)

AF:

0.574

AC:

22303

AN:

38886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

10290

20580

30870

41160

51450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.569

AC:

86559

AN:

152070

Hom.:

24665

Cov.:

AF XY:

0.566

AC XY:

42083

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.573

AC:

23751

AN:

41456

American (AMR)

AF:

0.616

AC:

9418

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2047

AN:

3466

East Asian (EAS)

AF:

0.597

AC:

3093

AN:

5184

South Asian (SAS)

AF:

0.620

AC:

2993

AN:

4826

European-Finnish (FIN)

AF:

0.491

AC:

5193

AN:

10572

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.561

AC:

38143

AN:

67970

Other (OTH)

AF:

0.585

AC:

1235

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1969

3938

5907

7876

9845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.549

Hom.:

10609

Bravo

AF:

0.584

Asia WGS

AF:

0.599

AC:

2081

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs509512

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over