5-153596765-T-C

Variant names:

• chr5-153596765-T-C
• rs778825
• NM_000827.4:c.221-50163T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000827.4(GRIA1):​c.221-50163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,144 control chromosomes in the GnomAD database, including 22,708 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 0.50 (22708 hom., cov: 33)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	NM_000827.4	MANE Select	c.221-50163T>C		intron	N/A	NP_000818.2
	GRIA1	NM_001258021.2		c.251-50163T>C		intron	N/A	NP_001244950.1
	GRIA1	NM_001258022.2		c.251-50163T>C		intron	N/A	NP_001244951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	ENST00000285900.10	TSL:1 MANE Select	c.221-50163T>C		intron	N/A	ENSP00000285900.4
	GRIA1	ENST00000340592.10	TSL:1	c.221-50163T>C		intron	N/A	ENSP00000339343.5
	GRIA1	ENST00000481559.6	TSL:1	n.362-50163T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75741 AN: 152026 Hom.: 22707 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.498 AC: 75751 AN: 152144 Hom.: 22708 Cov.: 33 AF XY: 0.501 AC XY: 37288 AN XY: 74400

African (AFR) AF: 0.142 AC: 5905 AN: 41526

American (AMR) AF: 0.560 AC: 8560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2115 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4150 AN: 5178

South Asian (SAS) AF: 0.533 AC: 2566 AN: 4814

European-Finnish (FIN) AF: 0.666 AC: 7038 AN: 10570

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43685 AN: 67982

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.555 Hom.: 4317

Bravo AF: 0.479

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		-0.088
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: rs778825; hg19: chr5-152976325;