chr1-36937413-A-G

Variant names:

• chr1-36937413-A-G
• rs481047
• NM_000831.4:c.116-46317T>C

Variant summary

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

The NM_000831.4(GRIK3):​c.116-46317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,196 control chromosomes in the GnomAD database, including 50,075 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 0.81 (50075 hom., cov: 32)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK3	NM_000831.4	MANE Select	c.116-46317T>C		intron	N/A	NP_000822.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK3	ENST00000373091.8	TSL:1 MANE Select	c.116-46317T>C		intron	N/A	ENSP00000362183.3
	GRIK3	ENST00000373093.4	TSL:1	c.116-46317T>C		intron	N/A	ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122735 AN: 152078 Hom.: 50050 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.807 AC: 122811 AN: 152196 Hom.: 50075 Cov.: 32 AF XY: 0.810 AC XY: 60274 AN XY: 74418

African (AFR) AF: 0.690 AC: 28652 AN: 41500

American (AMR) AF: 0.884 AC: 13522 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5101 AN: 5178

South Asian (SAS) AF: 0.864 AC: 4166 AN: 4820

European-Finnish (FIN) AF: 0.850 AC: 9007 AN: 10600

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57034 AN: 68014

Other (OTH) AF: 0.830 AC: 1752 AN: 2110

Alfa AF: 0.822 Hom.: 64394

Bravo AF: 0.803

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		0.14
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: rs481047; hg19: chr1-37403014;