rs457352

Positions:

• chr21-29872161-C-T

Variant summary

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

The NM_001330994.2(GRIK1):​c.118+67222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 150,110 control chromosomes in the GnomAD database, including 1,272 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 0.11 (1272 hom., cov: 29)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

Genes affected

GRIK1 (HGNC:4579): (glutamate ionotropic receptor kainate type subunit 1) 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 (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to alter the properties of ion flow. Alternative splicing, resulting in transcript variants encoding different isoforms, has been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK1	NM_001330994.2	c.118+67222G>A		intron_variant		ENST00000327783.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK1	ENST00000327783.9	c.118+67222G>A		intron_variant		5	NM_001330994.2	A1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16553 AN: 150044 Hom.: 1271 Cov.: 29

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.110 AC: 16558 AN: 150110 Hom.: 1272 Cov.: 29 AF XY: 0.116 AC XY: 8501 AN XY: 73058

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.125

Alfa AF: 0.105 Hom.: 118

Bravo AF: 0.115

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.82

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: rs457352; hg19: chr21-31244478;