1-36882636-C-T

Variant names:

• chr1-36882636-C-T
• rs17461259
• NM_000831.4:c.293-1745G>A

Variant summary

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

The NM_000831.4(GRIK3):​c.293-1745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,208 control chromosomes in the GnomAD database, including 336 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 0.056 (336 hom., cov: 32)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.293-1745G>A		intron_variant	Intron 2 of 15	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.293-1745G>A		intron_variant	Intron 2 of 15	1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.293-1745G>A		intron_variant	Intron 2 of 14	1		ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8512 AN: 152090 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0549

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00914

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0559 AC: 8504 AN: 152208 Hom.: 336 Cov.: 32 AF XY: 0.0562 AC XY: 4180 AN XY: 74408

African (AFR) AF: 0.0141 AC: 584 AN: 41540

American (AMR) AF: 0.0548 AC: 838 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.00873 AC: 42 AN: 4810

European-Finnish (FIN) AF: 0.102 AC: 1085 AN: 10590

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5432 AN: 68002

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0620 Hom.: 68

Bravo AF: 0.0508

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.48
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: rs17461259; hg19: chr1-37348237;