NM_001330994.2:c.119-79787T>G

Variant names:

• chr21-29773850-A-C
• rs455804
• NM_001330994.2:c.119-79787T>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.119-79787T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,080 control chromosomes in the GnomAD database, including 41,718 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 0.73 (41718 hom., cov: 31)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 35 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.119-79787T>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.119-79787T>G		intron_variant	Intron 1 of 17	5	NM_001330994.2	ENSP00000327687.4

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111653 AN: 151962 Hom.: 41684 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.735 AC: 111743 AN: 152080 Hom.: 41718 Cov.: 31 AF XY: 0.736 AC XY: 54728 AN XY: 74358

African (AFR) AF: 0.595 AC: 24639 AN: 41430

American (AMR) AF: 0.759 AC: 11598 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2779 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3610 AN: 5172

South Asian (SAS) AF: 0.788 AC: 3801 AN: 4822

European-Finnish (FIN) AF: 0.806 AC: 8537 AN: 10586

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54253 AN: 67998

Other (OTH) AF: 0.759 AC: 1604 AN: 2114

Alfa AF: 0.777 Hom.: 149967

Bravo AF: 0.724

Asia WGS AF: 0.730 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.36
PhyloP100		-0.88
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: rs455804; hg19: chr21-31146169;