21-29804448-A-T

Variant names:

• chr21-29804448-A-T
• rs460401
• NM_001330994.2:c.119-110385T>A

Variant summary

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

The NM_001330994.2(GRIK1):​c.119-110385T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,208 control chromosomes in the GnomAD database, including 49,284 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 0.80 (49284 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK1	NM_001330994.2	c.119-110385T>A		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.119-110385T>A		intron_variant	Intron 1 of 17	5	NM_001330994.2	ENSP00000327687.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 120970 AN: 151092 Hom.: 49255 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.801 AC: 121052 AN: 151208 Hom.: 49284 Cov.: 32 AF XY: 0.804 AC XY: 59388 AN XY: 73876

African (AFR) AF: 0.630 AC: 25920 AN: 41130

American (AMR) AF: 0.814 AC: 12347 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2903 AN: 3450

East Asian (EAS) AF: 0.789 AC: 4064 AN: 5154

South Asian (SAS) AF: 0.874 AC: 4179 AN: 4784

European-Finnish (FIN) AF: 0.884 AC: 9217 AN: 10432

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59647 AN: 67778

Other (OTH) AF: 0.821 AC: 1725 AN: 2102

Alfa AF: 0.840 Hom.: 6625

Bravo AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.012
DANN	Benign	0.44
PhyloP100		-2.5
Mutation Taster		=6/94	disease causing

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: rs460401; hg19: chr21-31176765;