NM_001330994.2:c.522A>C

Variant names:

• chr21-29689750-T-G
• rs363538
• NM_001330994.2:c.522A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001330994.2(GRIK1):​c.522A>C​(p.Thr174Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,154 control chromosomes in the GnomAD database, including 29,634 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 0.27 (9014 hom., cov: 32)
  • Exomes 𝑓: 0.14 (20620 hom.)
• Consequence: GRIK1 NM_001330994.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.80
• 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-5.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330994.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	NM_001330994.2	MANE Select	c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 18	NP_001317923.1	E7ENK3
	GRIK1	NM_001330993.2		c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 17	NP_001317922.1	E7EPY9
	GRIK1	NM_001320616.2		c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 17	NP_001307545.1	E9PD61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	ENST00000327783.9	TSL:5 MANE Select	c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 18	ENSP00000327687.4	E7ENK3
	GRIK1	ENST00000399907.6	TSL:1	c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 17	ENSP00000382791.1	P39086-1
	GRIK1	ENST00000389125.7	TSL:1	c.522A>C	p.Thr174Thr	synonymous	Exon 3 of 16	ENSP00000373777.3	P39086-2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41080 AN: 151856 Hom.: 8972 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.196 AC: 49317 AN: 251384 AF XY: 0.180

Gnomad AFR exome AF: 0.606

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.139 AC: 203553 AN: 1461180 Hom.: 20620 Cov.: 32 AF XY: 0.137 AC XY: 99451 AN XY: 726970

African (AFR) AF: 0.620 AC: 20727 AN: 33444

American (AMR) AF: 0.318 AC: 14204 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3137 AN: 26132

East Asian (EAS) AF: 0.326 AC: 12950 AN: 39698

South Asian (SAS) AF: 0.150 AC: 12912 AN: 86236

European-Finnish (FIN) AF: 0.131 AC: 6989 AN: 53418

Middle Eastern (MID) AF: 0.183 AC: 1053 AN: 5768

European-Non Finnish (NFE) AF: 0.110 AC: 121848 AN: 1111388

Other (OTH) AF: 0.161 AC: 9733 AN: 60372

GnomAD4 genome AF: 0.271 AC: 41183 AN: 151974 Hom.: 9014 Cov.: 32 AF XY: 0.269 AC XY: 19964 AN XY: 74288

African (AFR) AF: 0.596 AC: 24671 AN: 41384

American (AMR) AF: 0.270 AC: 4117 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1653 AN: 5168

South Asian (SAS) AF: 0.151 AC: 727 AN: 4810

European-Finnish (FIN) AF: 0.139 AC: 1474 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7567 AN: 67976

Other (OTH) AF: 0.222 AC: 469 AN: 2110

Alfa AF: 0.172 Hom.: 11849

Bravo AF: 0.300

Asia WGS AF: 0.258 AC: 901 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.58
PhyloP100		-5.8
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: rs363538; hg19: chr21-31062070; COSMIC: COSV58711098;