rs4693331

Positions:

• chr4-93620435-C-A
• chr4-93620435-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001510.4(GRID2):​c.2194-5834C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,992 control chromosomes in the GnomAD database, including 18,656 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 0.48 (18656 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID2	NM_001510.4	c.2194-5834C>A		intron_variant		ENST00000282020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID2	ENST00000282020.9	c.2194-5834C>A		intron_variant		1	NM_001510.4	P1
GRID2	ENST00000510992.5	c.1909-5834C>A		intron_variant		1
GRID2	ENST00000611049.4	c.1951-5834C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73468 AN: 151874 Hom.: 18654 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.484 AC: 73499 AN: 151992 Hom.: 18656 Cov.: 32 AF XY: 0.484 AC XY: 35945 AN XY: 74280

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.535

Alfa AF: 0.513 Hom.: 5051

Bravo AF: 0.480

Asia WGS AF: 0.585 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs4693331; hg19: chr4-94541586;