5-153655965-A-G

Variant names:

• chr5-153655965-A-G
• rs2963944
• NM_000827.4:c.699+93A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 67

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: ClinGen
• intellectual developmental disorder, autosomal recessive 76

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	NM_000827.4	MANE Select	c.699+93A>G		intron	N/A	NP_000818.2	P42261-1
	GRIA1	NM_001258021.2		c.729+93A>G		intron	N/A	NP_001244950.1	P42261-5
	GRIA1	NM_001258022.2		c.729+93A>G		intron	N/A	NP_001244951.1	P42261-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	ENST00000285900.10	TSL:1 MANE Select	c.699+93A>G		intron	N/A	ENSP00000285900.4	P42261-1
	GRIA1	ENST00000340592.10	TSL:1	c.699+93A>G		intron	N/A	ENSP00000339343.5	P42261-2
	GRIA1	ENST00000481559.6	TSL:1	n.840+93A>G		intron	N/A

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

African (AFR) AF: 0.144 AC: 3222 AN: 22400

American (AMR) AF: 0.241 AC: 10360 AN: 43028

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 6309 AN: 22228

East Asian (EAS) AF: 0.0177 AC: 652 AN: 36918

South Asian (SAS) AF: 0.141 AC: 10508 AN: 74500

European-Finnish (FIN) AF: 0.332 AC: 16317 AN: 49188

Middle Eastern (MID) AF: 0.237 AC: 1102 AN: 4644

European-Non Finnish (NFE) AF: 0.332 AC: 195337 AN: 588504

Other (OTH) AF: 0.285 AC: 11834 AN: 41452

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

African (AFR) AF: 0.149 AC: 6162 AN: 41480

American (AMR) AF: 0.269 AC: 4107 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3468

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5168

South Asian (SAS) AF: 0.134 AC: 645 AN: 4816

European-Finnish (FIN) AF: 0.326 AC: 3440 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23067 AN: 67930

Other (OTH) AF: 0.257 AC: 542 AN: 2108

Alfa AF: 0.182 Hom.: 441

Bravo AF: 0.254

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2963944; hg19: chr5-153035525;