chr21-29689750-T-G

Position:

• chr21-29689750-T-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.522A>C	p.Thr174Thr	synonymous_variant	3/18	ENST00000327783.9	NP_001317923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9	c.522A>C	p.Thr174Thr	synonymous_variant	3/18	5	NM_001330994.2	ENSP00000327687.4

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

GnomAD3 exomes AF: 0.196 AC: 49317 AN: 251384 Hom.: 7320 AF XY: 0.180 AC XY: 24402 AN XY: 135856

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 SAS exome AF: 0.151

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

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.161

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

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.222

Alfa AF: 0.140 Hom.: 4600

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.58

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: rs363538; hg19: chr21-31062070; COSMIC: COSV58711098;