chr21-29543953-C-T

Variant names:

• chr21-29543953-C-T
• rs2186305
• NM_001330994.2:c.2608-6069G>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.2608-6069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,018 control chromosomes in the GnomAD database, including 32,584 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 0.65 (32584 hom., cov: 32)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• 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]

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

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 (SAS) allele frequency at 95% confidence interval = 0.702 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.2608-6069G>A		intron	N/A	NP_001317923.1
	GRIK1	NM_001330993.2		c.2563-6069G>A		intron	N/A	NP_001317922.1
	GRIK1	NM_001320616.2		c.2608-6568G>A		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.2608-6069G>A		intron	N/A	ENSP00000327687.4
	GRIK1	ENST00000389125.7	TSL:1	c.2563-6568G>A		intron	N/A	ENSP00000373777.3
	GRIK1	ENST00000399914.5	TSL:5	c.2563-6069G>A		intron	N/A	ENSP00000382798.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98517 AN: 151900 Hom.: 32565 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.649 AC: 98591 AN: 152018 Hom.: 32584 Cov.: 32 AF XY: 0.651 AC XY: 48363 AN XY: 74296

African (AFR) AF: 0.513 AC: 21245 AN: 41438

American (AMR) AF: 0.686 AC: 10482 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3472

East Asian (EAS) AF: 0.697 AC: 3584 AN: 5144

South Asian (SAS) AF: 0.722 AC: 3478 AN: 4818

European-Finnish (FIN) AF: 0.697 AC: 7357 AN: 10554

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47774 AN: 67996

Other (OTH) AF: 0.644 AC: 1356 AN: 2106

Alfa AF: 0.682 Hom.: 44092

Bravo AF: 0.642

Asia WGS AF: 0.677 AC: 2354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.37
PhyloP100		-0.39
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: rs2186305; hg19: chr21-30916274;