rs10041275

Variant names:

• chr5-153682601-T-C
• rs10041275
• NM_000827.4:c.1030-3624T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-153682601-T-C
• chr5-153682601-T-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.1030-3624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,908 control chromosomes in the GnomAD database, including 8,890 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 0.32 (8890 hom., cov: 32)
• Consequence: GRIA1 NM_000827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 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.1030-3624T>C		intron	N/A	NP_000818.2
	GRIA1	NM_001258021.2		c.1060-3624T>C		intron	N/A	NP_001244950.1
	GRIA1	NM_001258022.2		c.1060-3624T>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.1030-3624T>C		intron	N/A	ENSP00000285900.4
	GRIA1	ENST00000340592.10	TSL:1	c.1030-3624T>C		intron	N/A	ENSP00000339343.5
	GRIA1	ENST00000481559.6	TSL:1	n.1171-3624T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49277 AN: 151790 Hom.: 8888 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.325 AC: 49303 AN: 151908 Hom.: 8890 Cov.: 32 AF XY: 0.325 AC XY: 24132 AN XY: 74204

African (AFR) AF: 0.451 AC: 18676 AN: 41408

American (AMR) AF: 0.269 AC: 4108 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2701 AN: 5112

South Asian (SAS) AF: 0.418 AC: 2011 AN: 4808

European-Finnish (FIN) AF: 0.257 AC: 2715 AN: 10554

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16829 AN: 67972

Other (OTH) AF: 0.339 AC: 714 AN: 2108

Alfa AF: 0.273 Hom.: 18437

Bravo AF: 0.332

Asia WGS AF: 0.447 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.86
PhyloP100		-0.080
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: rs10041275; hg19: chr5-153062161;