rs2195450

Variant names:

• chr5-153491449-G-A
• rs2195450
• NM_000827.4:c.82+479G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000827.4(GRIA1):​c.82+479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 320,324 control chromosomes in the GnomAD database, including 7,915 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 0.17 (2870 hom., cov: 31)
  • Exomes 𝑓: 0.24 (5045 hom.)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 16 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 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.82+479G>A		intron	N/A	NP_000818.2
	GRIA1	NM_001364166.2		c.24+117G>A		intron	N/A	NP_001351095.1
	GRIA1	NM_001114183.2		c.82+479G>A		intron	N/A	NP_001107655.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	ENST00000285900.10	TSL:1 MANE Select	c.82+479G>A		intron	N/A	ENSP00000285900.4
	GRIA1	ENST00000340592.10	TSL:1	c.82+479G>A		intron	N/A	ENSP00000339343.5
	GRIA1	ENST00000481559.6	TSL:1	n.223+1612G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26218 AN: 151912 Hom.: 2870 Cov.: 31

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.242 AC: 40657 AN: 168294 Hom.: 5045 AF XY: 0.240 AC XY: 19509 AN XY: 81262

African (AFR) AF: 0.0414 AC: 126 AN: 3044

American (AMR) AF: 0.147 AC: 182 AN: 1240

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 285 AN: 1192

East Asian (EAS) AF: 0.115 AC: 110 AN: 960

South Asian (SAS) AF: 0.0943 AC: 348 AN: 3692

European-Finnish (FIN) AF: 0.167 AC: 59 AN: 354

Middle Eastern (MID) AF: 0.224 AC: 74 AN: 330

European-Non Finnish (NFE) AF: 0.252 AC: 38223 AN: 151892

Other (OTH) AF: 0.224 AC: 1250 AN: 5590

GnomAD4 genome AF: 0.172 AC: 26218 AN: 152030 Hom.: 2870 Cov.: 31 AF XY: 0.169 AC XY: 12538 AN XY: 74292

African (AFR) AF: 0.0475 AC: 1969 AN: 41486

American (AMR) AF: 0.180 AC: 2751 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3470

East Asian (EAS) AF: 0.123 AC: 634 AN: 5146

South Asian (SAS) AF: 0.0909 AC: 437 AN: 4808

European-Finnish (FIN) AF: 0.204 AC: 2153 AN: 10568

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16838 AN: 67972

Other (OTH) AF: 0.181 AC: 382 AN: 2108

Alfa AF: 0.208 Hom.: 455

Bravo AF: 0.168

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.61
PromoterAI		-0.0081	Neutral
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: rs2195450; hg19: chr5-152871009;