rs472188

chr1-36938357-G-A

Variant summary

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

The NM_000831.4(GRIK3):c.116-47261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,150 control chromosomes in the GnomAD database, including 3,992 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 0.20 (3992 hom., cov: 33)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

Genes affected

GRIK3 (HGNC:4581): (glutamate ionotropic receptor kainate type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK3	NM_000831.4	c.116-47261C>T		intron_variant		ENST00000373091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK3	ENST00000373091.8	c.116-47261C>T		intron_variant		1	NM_000831.4	P1
GRIK3	ENST00000373093.4	c.116-47261C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30120 AN: 152032 Hom.: 3970 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.198 AC: 30181 AN: 152150 Hom.: 3992 Cov.: 33 AF XY: 0.192 AC XY: 14274 AN XY: 74410

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.192

Alfa AF: 0.0895 Hom.: 168

Bravo AF: 0.214

Asia WGS AF: 0.100 AC: 348 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	6.0
Dann	Benign	0.60

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: rs472188; hg19: chr1-37403958;