Variant 21-29598863-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001330994.2(GRIK1):c.1173C>T(p.Asp391Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,561,992 control chromosomes in the GnomAD database, including 21,848 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 0.17 ( 2498 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19350 hom. )

Consequence

GRIK1
NM_001330994.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.874

Variant links:

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 links:

GRIK1 (HGNC:):

GRIK1 links:

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]

BACH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.874 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK1	NM_001330994.2 linkuse as main transcript	c.1173C>T	p.Asp391Asp	synonymous_variant	8/18	ENST00000327783.9	NP_001317923.1	E7ENK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK1	ENST00000327783.9 linkuse as main transcript	c.1173C>T	p.Asp391Asp	synonymous_variant	8/18	5	NM_001330994.2	ENSP00000327687.4		E7ENK3

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26081

AN:

151942

Hom.:

2488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.182

AC:

44856

AN:

245984

Hom.:

5224

AF XY:

0.173

AC XY:

23026

AN XY:

133146

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.154

AC:

216953

AN:

1409932

Hom.:

19350

Cov.:

AF XY:

0.153

AC XY:

107889

AN XY:

704206

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.339

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.172

AC:

26116

AN:

152060

Hom.:

2498

Cov.:

AF XY:

0.172

AC XY:

12808

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.143

Hom.:

934

Bravo

AF:

0.183

Asia WGS

AF:

0.296

AC:

1027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.0

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over