rs2154490

chr21-29543641-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330994.2(GRIK1):c.2608-5757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,014 control chromosomes in the GnomAD database, including 43,442 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 0.75 (43442 hom., cov: 31)
• Consequence: GRIK1 NM_001330994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK1	NM_001330994.2	c.2608-5757T>C		intron_variant		ENST00000327783.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK1	ENST00000327783.9	c.2608-5757T>C		intron_variant		5	NM_001330994.2	A1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114650 AN: 151896 Hom.: 43394 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.755 AC: 114751 AN: 152014 Hom.: 43442 Cov.: 31 AF XY: 0.757 AC XY: 56248 AN XY: 74290

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.749

Alfa AF: 0.741 Hom.: 7135

Bravo AF: 0.762

Asia WGS AF: 0.774 AC: 2690 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	0.0060
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2154490; hg19: chr21-30915962;