5-153655965-A-G

Position:

• chr5-153655965-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000827.4(GRIA1):​c.699+93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,034,850 control chromosomes in the GnomAD database, including 47,203 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 0.26 (5964 hom., cov: 31)
  • Exomes 𝑓: 0.29 (41239 hom.)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	c.699+93A>G		intron_variant		ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.699+93A>G		intron_variant		1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39506 AN: 151868 Hom.: 5964 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.290 AC: 255641 AN: 882862 Hom.: 41239 AF XY: 0.285 AC XY: 132060 AN XY: 462846

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.260 AC: 39513 AN: 151988 Hom.: 5964 Cov.: 31 AF XY: 0.254 AC XY: 18892 AN XY: 74268

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.257

Alfa AF: 0.184 Hom.: 435

Bravo AF: 0.254

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2963944; hg19: chr5-153035525;