chr5-153695544-A-G

Variant names:

• chr5-153695544-A-G
• rs4530817
• NM_000827.4:c.1135-2500A>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.1135-2500A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,064 control chromosomes in the GnomAD database, including 10,725 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 (10725 hom., cov: 33)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA1	NM_000827.4	c.1135-2500A>G		intron_variant	Intron 8 of 15	ENST00000285900.10	NP_000818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA1	ENST00000285900.10	c.1135-2500A>G		intron_variant	Intron 8 of 15	1	NM_000827.4	ENSP00000285900.4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55571 AN: 151946 Hom.: 10707 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.366 AC: 55626 AN: 152064 Hom.: 10725 Cov.: 33 AF XY: 0.373 AC XY: 27691 AN XY: 74312

African (AFR) AF: 0.242 AC: 10037 AN: 41494

American (AMR) AF: 0.441 AC: 6737 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2261 AN: 5154

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4749 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27285 AN: 67968

Other (OTH) AF: 0.359 AC: 757 AN: 2110

Alfa AF: 0.400 Hom.: 10097

Bravo AF: 0.361

Asia WGS AF: 0.427 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.28
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: rs4530817; hg19: chr5-153075104;