rs535620

Positions:

• chr1-36954240-A-G
• chr1-36954240-A-T

Variant summary

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

The NM_000831.4(GRIK3):​c.116-63144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,086 control chromosomes in the GnomAD database, including 33,921 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 0.66 (33921 hom., cov: 33)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK3	NM_000831.4	c.116-63144T>C		intron_variant		ENST00000373091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK3	ENST00000373091.8	c.116-63144T>C		intron_variant		1	NM_000831.4	P1
GRIK3	ENST00000373093.4	c.116-63144T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100611 AN: 151968 Hom.: 33877 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.662 AC: 100713 AN: 152086 Hom.: 33921 Cov.: 33 AF XY: 0.667 AC XY: 49610 AN XY: 74342

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.682

Alfa AF: 0.679 Hom.: 48585

Bravo AF: 0.666

Asia WGS AF: 0.843 AC: 2928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs535620; hg19: chr1-37419841;