rs3738085

Positions:

• chr1-36869950-G-A
• chr1-36869950-G-T

Variant summary

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

The NM_000831.4(GRIK3):​c.733-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 650,926 control chromosomes in the GnomAD database, including 268,510 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 0.86 (56992 hom., cov: 33)
  • Exomes 𝑓: 0.92 (211518 hom.)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.733-149C>T		intron_variant		ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.733-149C>T		intron_variant		1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.733-149C>T		intron_variant		1		ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130553 AN: 152138 Hom.: 56979 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.876

GnomAD4 exome AF: 0.920 AC: 458573 AN: 498670 Hom.: 211518 AF XY: 0.921 AC XY: 245153 AN XY: 266282

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.943

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.971

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.936

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.858 AC: 130609 AN: 152256 Hom.: 56992 Cov.: 33 AF XY: 0.861 AC XY: 64077 AN XY: 74438

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.935

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.877

Alfa AF: 0.899 Hom.: 26429

Bravo AF: 0.848

Asia WGS AF: 0.902 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.8
DANN	Benign	0.59

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: rs3738085; hg19: chr1-37335551;