rs363430

Variant names:

• chr21-29598863-G-A
• rs363430
• NM_001330994.2:c.1173C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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]

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]

GRIK1-AS2 (HGNC:1282): (GRIK1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.1173C>T	p.Asp391Asp	synonymous_variant	Exon 8 of 18	ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.1173C>T	p.Asp391Asp	synonymous_variant	Exon 8 of 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

GnomAD2 exomes AF: 0.182 AC: 44856 AN: 245984 AF XY: 0.173

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 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

African (AFR) AF: 0.177 AC: 5693 AN: 32228

American (AMR) AF: 0.339 AC: 14691 AN: 43396

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2875 AN: 25798

East Asian (EAS) AF: 0.336 AC: 13062 AN: 38922

South Asian (SAS) AF: 0.183 AC: 15307 AN: 83862

European-Finnish (FIN) AF: 0.121 AC: 6441 AN: 53232

Middle Eastern (MID) AF: 0.150 AC: 850 AN: 5652

European-Non Finnish (NFE) AF: 0.139 AC: 148553 AN: 1068374

Other (OTH) AF: 0.162 AC: 9481 AN: 58468

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

African (AFR) AF: 0.177 AC: 7353 AN: 41466

American (AMR) AF: 0.267 AC: 4079 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3464

East Asian (EAS) AF: 0.331 AC: 1716 AN: 5180

South Asian (SAS) AF: 0.190 AC: 915 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1316 AN: 10578

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9714 AN: 67980

Other (OTH) AF: 0.172 AC: 364 AN: 2114

Alfa AF: 0.151 Hom.: 1377

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
PhyloP100		0.87
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: rs363430; hg19: chr21-30971183; COSMIC: COSV58713542;