21-29854785-G-C

Variant names:

• chr21-29854785-G-C
• rs469472
• NM_001330994.2:c.118+84598C>G

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+84598C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,016 control chromosomes in the GnomAD database, including 8,528 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 0.32 (8528 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.118+84598C>G		intron_variant	Intron 1 of 17	ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.118+84598C>G		intron_variant	Intron 1 of 17	5	NM_001330994.2	ENSP00000327687.4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48777 AN: 151898 Hom.: 8514 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.321 AC: 48832 AN: 152016 Hom.: 8528 Cov.: 32 AF XY: 0.320 AC XY: 23804 AN XY: 74322

African (AFR) AF: 0.456 AC: 18886 AN: 41414

American (AMR) AF: 0.314 AC: 4794 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2380 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1917 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10586

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17198 AN: 67984

Other (OTH) AF: 0.298 AC: 629 AN: 2108

Alfa AF: 0.132 Hom.: 206

Bravo AF: 0.339

Asia WGS AF: 0.440 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.27
PhyloP100		-1.8
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: rs469472; hg19: chr21-31227102;