rs726002

Positions:

• chr21-29678973-G-A

Variant summary

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

The NM_001330994.2(GRIK1):​c.545-5809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 152,226 control chromosomes in the GnomAD database, including 386 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 0.050 (386 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.545-5809C>T		intron_variant		ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.545-5809C>T		intron_variant		5	NM_001330994.2	ENSP00000327687	A1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7628 AN: 152108 Hom.: 387 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0501 AC: 7632 AN: 152226 Hom.: 386 Cov.: 32 AF XY: 0.0494 AC XY: 3674 AN XY: 74436

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0382 Hom.: 32

Bravo AF: 0.0540

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.53

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: rs726002; hg19: chr21-31051293;