5-153650400-T-A

Variant names:

• chr5-153650400-T-A
• NM_000827.4:c.531T>A
• GRIA1 p.Ile177Ile

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000827.4(GRIA1):​c.531T>A​(p.Ile177Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I177I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GRIA1 NM_000827.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• Publications: 0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: ClinGen
• intellectual developmental disorder, autosomal recessive 76

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.861 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	NM_000827.4	MANE Select	c.531T>A	p.Ile177Ile	synonymous	Exon 4 of 16	NP_000818.2	P42261-1
	GRIA1	NM_001258021.2		c.561T>A	p.Ile187Ile	synonymous	Exon 4 of 16	NP_001244950.1	P42261-5
	GRIA1	NM_001258022.2		c.561T>A	p.Ile187Ile	synonymous	Exon 4 of 16	NP_001244951.1	P42261-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA1	ENST00000285900.10	TSL:1 MANE Select	c.531T>A	p.Ile177Ile	synonymous	Exon 4 of 16	ENSP00000285900.4	P42261-1
	GRIA1	ENST00000340592.10	TSL:1	c.531T>A	p.Ile177Ile	synonymous	Exon 4 of 16	ENSP00000339343.5	P42261-2
	GRIA1	ENST00000481559.6	TSL:1	n.672T>A		non_coding_transcript_exon	Exon 4 of 11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.86

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-153029960;