rs363430

Positions:

• chr21-29598863-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001330994.2(GRIK1):​c.1173C>T​(p.Asp391Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,561,992 control chromosomes in the GnomAD database, including 21,848 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 0.17 (2498 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19350 hom.)
• Consequence: GRIK1 NM_001330994.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

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]

GRIK1 (HGNC:):

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.874 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.1173C>T	p.Asp391Asp	synonymous_variant	8/18	ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.1173C>T	p.Asp391Asp	synonymous_variant	8/18	5	NM_001330994.2	ENSP00000327687.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26081 AN: 151942 Hom.: 2488 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.182 AC: 44856 AN: 245984 Hom.: 5224 AF XY: 0.173 AC XY: 23026 AN XY: 133146

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.295

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.154 AC: 216953 AN: 1409932 Hom.: 19350 Cov.: 24 AF XY: 0.153 AC XY: 107889 AN XY: 704206

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.172 AC: 26116 AN: 152060 Hom.: 2498 Cov.: 32 AF XY: 0.172 AC XY: 12808 AN XY: 74332

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.172

Alfa AF: 0.143 Hom.: 934

Bravo AF: 0.183

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.0
DANN	Benign	0.78

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: rs363430; hg19: chr21-30971183; COSMIC: COSV58713542;