chr1-36869484-C-A

Variant names:

• chr1-36869484-C-A
• rs574214
• NM_000831.4:c.786+264G>T

Variant summary

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

The NM_000831.4(GRIK3):​c.786+264G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,254 control chromosomes in the GnomAD database, including 61,013 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 0.89 (61013 hom., cov: 33)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.786+264G>T		intron_variant	Intron 5 of 15	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.786+264G>T		intron_variant	Intron 5 of 15	1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.786+264G>T		intron_variant	Intron 5 of 14	1		ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135867 AN: 152136 Hom.: 60966 Cov.: 33

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.893 AC: 135975 AN: 152254 Hom.: 61013 Cov.: 33 AF XY: 0.896 AC XY: 66685 AN XY: 74450

African (AFR) AF: 0.794 AC: 32948 AN: 41522

American (AMR) AF: 0.947 AC: 14476 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2974 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5112 AN: 5182

South Asian (SAS) AF: 0.941 AC: 4543 AN: 4830

European-Finnish (FIN) AF: 0.933 AC: 9898 AN: 10614

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.927 AC: 63042 AN: 68026

Other (OTH) AF: 0.905 AC: 1915 AN: 2116

Alfa AF: 0.915 Hom.: 242681

Bravo AF: 0.889

Asia WGS AF: 0.945 AC: 3284 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		1.5
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: rs574214; hg19: chr1-37335085;