chr5-153803165-T-G

Variant names:

• chr5-153803165-T-G
• rs1461225
• NM_000827.4:c.2520+675T>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.2520+675T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,052 control chromosomes in the GnomAD database, including 12,213 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 0.37 (12213 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.2520+675T>G		intron_variant	Intron 15 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.2520+675T>G		intron_variant	Intron 15 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55811 AN: 151934 Hom.: 12181 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 55893 AN: 152052 Hom.: 12213 Cov.: 32 AF XY: 0.372 AC XY: 27628 AN XY: 74328

African (AFR) AF: 0.508 AC: 21046 AN: 41436

American (AMR) AF: 0.446 AC: 6812 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3472

East Asian (EAS) AF: 0.908 AC: 4689 AN: 5166

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4820

European-Finnish (FIN) AF: 0.269 AC: 2845 AN: 10588

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16752 AN: 67968

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.284 Hom.: 11296

Bravo AF: 0.390

Asia WGS AF: 0.582 AC: 2021 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.18
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: rs1461225; hg19: chr5-153182725;