rs2832438

chr21-29765618-T-Cchr21-29765618-T-A

Variant summary

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

The NM_001330994.2(GRIK1):c.119-71555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,982 control chromosomes in the GnomAD database, including 4,253 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 0.20 (4253 hom., cov: 31)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

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 (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK1	NM_001330994.2	c.119-71555A>G		intron_variant		ENST00000327783.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK1	ENST00000327783.9	c.119-71555A>G		intron_variant		5	NM_001330994.2	A1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29964 AN: 151864 Hom.: 4231 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.198 AC: 30022 AN: 151982 Hom.: 4253 Cov.: 31 AF XY: 0.193 AC XY: 14358 AN XY: 74328

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.166

Alfa AF: 0.130 Hom.: 2321

Bravo AF: 0.208

Asia WGS AF: 0.154 AC: 533 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	0.016
Dann	Benign	0.32

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: rs2832438; hg19: chr21-31137937;