rs457531

Positions:

• chr21-29899199-C-T
• chr21-29899199-C-G

Variant summary

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

The NM_001330994.2(GRIK1):​c.118+40184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,154 control chromosomes in the GnomAD database, including 4,247 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 0.22 (4247 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.118+40184G>A		intron_variant		ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.118+40184G>A		intron_variant		5	NM_001330994.2	ENSP00000327687	A1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33619 AN: 152036 Hom.: 4237 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.221 AC: 33659 AN: 152154 Hom.: 4247 Cov.: 32 AF XY: 0.224 AC XY: 16641 AN XY: 74390

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0992 Hom.: 166

Bravo AF: 0.230

Asia WGS AF: 0.259 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.27

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: rs457531; hg19: chr21-31271516;