rs457352

Variant names:

• chr21-29872161-C-T
• rs457352
• NM_001330994.2:c.118+67222G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330994.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	NM_001330994.2	MANE Select	c.118+67222G>A		intron	N/A	NP_001317923.1	E7ENK3
	GRIK1	NM_001330993.2		c.118+67222G>A		intron	N/A	NP_001317922.1	E7EPY9
	GRIK1	NM_001320616.2		c.118+67222G>A		intron	N/A	NP_001307545.1	E9PD61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	ENST00000327783.9	TSL:5 MANE Select	c.118+67222G>A		intron	N/A	ENSP00000327687.4	E7ENK3
	GRIK1	ENST00000399907.6	TSL:1	c.118+67222G>A		intron	N/A	ENSP00000382791.1	P39086-1
	GRIK1	ENST00000389125.7	TSL:1	c.118+67222G>A		intron	N/A	ENSP00000373777.3	P39086-2

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

African (AFR) AF: 0.0422 AC: 1725 AN: 40892

American (AMR) AF: 0.177 AC: 2671 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1779 AN: 5064

South Asian (SAS) AF: 0.271 AC: 1292 AN: 4760

European-Finnish (FIN) AF: 0.0930 AC: 916 AN: 9854

Middle Eastern (MID) AF: 0.123 AC: 35 AN: 284

European-Non Finnish (NFE) AF: 0.109 AC: 7362 AN: 67718

Other (OTH) AF: 0.125 AC: 259 AN: 2072

Alfa AF: 0.102 Hom.: 118

Bravo AF: 0.115

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.69
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: rs457352; hg19: chr21-31244478;