5-153533944-G-T

Variant names:

• chr5-153533944-G-T
• rs1463747
• NM_000827.4:c.220+39879G>T

Variant summary

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

The NM_000827.4(GRIA1):​c.220+39879G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,128 control chromosomes in the GnomAD database, including 12,952 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 0.38 (12952 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 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.220+39879G>T		intron	N/A	NP_000818.2
	GRIA1	NM_001258021.2		c.250+39879G>T		intron	N/A	NP_001244950.1
	GRIA1	NM_001258022.2		c.250+39879G>T		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.220+39879G>T		intron	N/A	ENSP00000285900.4
	GRIA1	ENST00000340592.10	TSL:1	c.220+39879G>T		intron	N/A	ENSP00000339343.5
	GRIA1	ENST00000481559.6	TSL:1	n.361+39879G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57246 AN: 152010 Hom.: 12954 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.376 AC: 57259 AN: 152128 Hom.: 12952 Cov.: 32 AF XY: 0.375 AC XY: 27880 AN XY: 74358

African (AFR) AF: 0.155 AC: 6434 AN: 41530

American (AMR) AF: 0.309 AC: 4721 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3464

East Asian (EAS) AF: 0.143 AC: 739 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1666 AN: 4822

European-Finnish (FIN) AF: 0.538 AC: 5683 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34970 AN: 67968

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.454 Hom.: 52003

Bravo AF: 0.350

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.66
PhyloP100		-0.78
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: rs1463747; hg19: chr5-152913504;