rs363512

chr21-29678497-G-Achr21-29678497-G-T

Variant summary

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

The NM_001330994.2(GRIK1):c.545-5333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,984 control chromosomes in the GnomAD database, including 1,900 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 0.13 (1900 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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 = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK1	NM_001330994.2	c.545-5333C>T		intron_variant		ENST00000327783.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK1	ENST00000327783.9	c.545-5333C>T		intron_variant		5	NM_001330994.2	A1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19942 AN: 151866 Hom.: 1895 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0777

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.131 AC: 19971 AN: 151984 Hom.: 1900 Cov.: 32 AF XY: 0.131 AC XY: 9767 AN XY: 74294

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0777

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0754 Hom.: 1180

Bravo AF: 0.145

Asia WGS AF: 0.159 AC: 553 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	0.99
Dann	Benign	0.45

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: rs363512; hg19: chr21-31050817;