rs933117

Variant names:

• chr21-29728478-G-A
• rs933117
• NM_001330994.2:c.119-34415C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-29728478-G-A
• chr21-29728478-G-C
• chr21-29728478-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.119-34415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,168 control chromosomes in the GnomAD database, including 734 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 0.092 (734 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.119-34415C>T		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.119-34415C>T		intron_variant	Intron 1 of 17	5	NM_001330994.2	ENSP00000327687.4

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13967 AN: 152050 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0864

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

GnomAD4 genome AF: 0.0919 AC: 13982 AN: 152168 Hom.: 734 Cov.: 32 AF XY: 0.0915 AC XY: 6805 AN XY: 74400

African (AFR) AF: 0.130 AC: 5411 AN: 41506

American (AMR) AF: 0.117 AC: 1784 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.104 AC: 539 AN: 5162

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4818

European-Finnish (FIN) AF: 0.0968 AC: 1026 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4705 AN: 67998

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0764 Hom.: 2215

Bravo AF: 0.0976

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.42
PhyloP100		-0.51
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: rs933117; hg19: chr21-31100797;