rs2178865

Variant names:

• chr21-29755877-G-A
• rs2178865
• NM_001330994.2:c.119-61814C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-29755877-G-A
• chr21-29755877-G-C
• chr21-29755877-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330994.2(GRIK1):​c.119-61814C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,006 control chromosomes in the GnomAD database, including 20,645 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 0.49 (20645 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 3 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]

GRIK1-AS1 (HGNC:16458): (GRIK1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	NM_001330994.2	MANE Select	c.119-61814C>T		intron	N/A	NP_001317923.1
	GRIK1	NM_001330993.2		c.119-61814C>T		intron	N/A	NP_001317922.1
	GRIK1	NM_001320616.2		c.119-61814C>T		intron	N/A	NP_001307545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK1	ENST00000327783.9	TSL:5 MANE Select	c.119-61814C>T		intron	N/A	ENSP00000327687.4
	GRIK1	ENST00000399907.6	TSL:1	c.119-61814C>T		intron	N/A	ENSP00000382791.1
	GRIK1	ENST00000389125.7	TSL:1	c.119-61814C>T		intron	N/A	ENSP00000373777.3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74477 AN: 151888 Hom.: 20646 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.490 AC: 74488 AN: 152006 Hom.: 20645 Cov.: 32 AF XY: 0.494 AC XY: 36716 AN XY: 74308

African (AFR) AF: 0.212 AC: 8804 AN: 41470

American (AMR) AF: 0.522 AC: 7976 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3470

East Asian (EAS) AF: 0.470 AC: 2421 AN: 5156

South Asian (SAS) AF: 0.632 AC: 3039 AN: 4808

European-Finnish (FIN) AF: 0.596 AC: 6300 AN: 10564

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41816 AN: 67940

Other (OTH) AF: 0.546 AC: 1152 AN: 2108

Alfa AF: 0.569 Hom.: 75841

Bravo AF: 0.468

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.71
PhyloP100		0.19
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: rs2178865; hg19: chr21-31128196;