rs9390754

Positions:

• chr6-101517038-A-G

Variant summary

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

The NM_021956.5(GRIK2):​c.116-104911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,984 control chromosomes in the GnomAD database, including 4,618 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 0.20 (4618 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

GRIK2 (HGNC:4580): (glutamate ionotropic receptor kainate type subunit 2) 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. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

GRIK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.116-104911A>G		intron_variant		ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.116-104911A>G		intron_variant		5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30720 AN: 151866 Hom.: 4620 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.202 AC: 30727 AN: 151984 Hom.: 4618 Cov.: 32 AF XY: 0.205 AC XY: 15264 AN XY: 74280

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.0870

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.173

Alfa AF: 0.119 Hom.: 1861

Bravo AF: 0.215

Asia WGS AF: 0.307 AC: 1066 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9390754; hg19: chr6-101964914;