rs1433666

Variant names:

• chr4-93331209-G-A
• rs1433666
• NM_001510.4:c.1246-64398G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-93331209-G-A
• chr4-93331209-G-C

Variant summary

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

The NM_001510.4(GRID2):​c.1246-64398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 148,332 control chromosomes in the GnomAD database, including 28,231 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 0.62 (28231 hom., cov: 24)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 6 publications found

Genes affected

GRID2 (HGNC:4576): (glutamate ionotropic receptor delta type subunit 2) The protein encoded by this gene is a member of the family of ionotropic glutamate receptors which are the predominant excitatory neurotransmitter receptors in the mammalian brain. The encoded protein is a multi-pass membrane protein that is expressed selectively in cerebellar Purkinje cells. A point mutation in the mouse ortholog, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. This protein also plays a role in synapse organization between parallel fibers and Purkinje cells. Alternate splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause cerebellar ataxia in humans. [provided by RefSeq, Apr 2014]

GRID2 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 18

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

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 (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.1246-64398G>A		intron_variant	Intron 8 of 15	ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.1246-64398G>A		intron_variant	Intron 8 of 15	1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000611049.4	c.1003-64398G>A		intron_variant	Intron 6 of 13	1		ENSP00000483084.1
GRID2	ENST00000510992.5	c.961-64398G>A		intron_variant	Intron 7 of 14	1		ENSP00000421257.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 91523 AN: 148224 Hom.: 28225 Cov.: 24

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.546

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.617 AC: 91558 AN: 148332 Hom.: 28231 Cov.: 24 AF XY: 0.618 AC XY: 44611 AN XY: 72136

African (AFR) AF: 0.690 AC: 27749 AN: 40206

American (AMR) AF: 0.560 AC: 8191 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1806 AN: 3458

East Asian (EAS) AF: 0.731 AC: 3619 AN: 4948

South Asian (SAS) AF: 0.596 AC: 2788 AN: 4674

European-Finnish (FIN) AF: 0.647 AC: 6423 AN: 9932

Middle Eastern (MID) AF: 0.546 AC: 155 AN: 284

European-Non Finnish (NFE) AF: 0.581 AC: 39069 AN: 67244

Other (OTH) AF: 0.595 AC: 1215 AN: 2042

Alfa AF: 0.580 Hom.: 40118

Bravo AF: 0.608

Asia WGS AF: 0.665 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.40
PhyloP100		-0.15
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: rs1433666; hg19: chr4-94252360;