rs6671364

Variant names:

• chr1-36812976-T-C
• rs6671364
• NM_000831.4:c.2091+4084A>G

Variant summary

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

The NM_000831.4(GRIK3):​c.2091+4084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,304 control chromosomes in the GnomAD database, including 435 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 0.064 (435 hom., cov: 32)
• Consequence: GRIK3 NM_000831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK3	NM_000831.4	c.2091+4084A>G		intron_variant	Intron 13 of 15	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8	c.2091+4084A>G		intron_variant	Intron 13 of 15	1	NM_000831.4	ENSP00000362183.3
GRIK3	ENST00000373093.4	c.2091+4084A>G		intron_variant	Intron 13 of 14	1		ENSP00000362185.4

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9756 AN: 152186 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0641 AC: 9756 AN: 152304 Hom.: 435 Cov.: 32 AF XY: 0.0616 AC XY: 4588 AN XY: 74474

African (AFR) AF: 0.0174 AC: 722 AN: 41572

American (AMR) AF: 0.0705 AC: 1079 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4818

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10618

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6712 AN: 68014

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0734 Hom.: 234

Bravo AF: 0.0619

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.60
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: rs6671364; hg19: chr1-37278577;