rs2156634

Variant summary

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

The NM_014619.5(GRIK4):​c.1275G>A​(p.Glu425Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,608,732 control chromosomes in the GnomAD database, including 592,800 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 58941 hom., cov: 32)
Exomes 𝑓: 0.86 ( 533859 hom. )

Consequence

GRIK4
NM_014619.5 splice_region, synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13
Variant links:
Genes affected
GRIK4 (HGNC:4582): (glutamate ionotropic receptor kainate type subunit 4) This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

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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=-0.4).
BP7
Synonymous conserved (PhyloP=3.13 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIK4NM_014619.5 linkc.1275G>A p.Glu425Glu splice_region_variant, synonymous_variant Exon 13 of 21 ENST00000527524.8 NP_055434.2 Q16099A0A8D9PH79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIK4ENST00000527524.8 linkc.1275G>A p.Glu425Glu splice_region_variant, synonymous_variant Exon 13 of 21 2 NM_014619.5 ENSP00000435648.2 Q16099
GRIK4ENST00000438375.2 linkc.1275G>A p.Glu425Glu splice_region_variant, synonymous_variant Exon 12 of 20 1 ENSP00000404063.2 Q16099
GRIK4ENST00000533291.5 linkn.1673G>A splice_region_variant, non_coding_transcript_exon_variant Exon 13 of 18 1
GRIK4ENST00000638419.1 linkc.1275G>A p.Glu425Glu splice_region_variant, synonymous_variant Exon 13 of 21 5 ENSP00000492086.1 Q16099

Frequencies

GnomAD3 genomes
AF:
0.879
AC:
133637
AN:
152066
Hom.:
58896
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.944
Gnomad AMI
AF:
0.838
Gnomad AMR
AF:
0.799
Gnomad ASJ
AF:
0.891
Gnomad EAS
AF:
0.913
Gnomad SAS
AF:
0.811
Gnomad FIN
AF:
0.884
Gnomad MID
AF:
0.880
Gnomad NFE
AF:
0.859
Gnomad OTH
AF:
0.864
GnomAD3 exomes
AF:
0.852
AC:
213793
AN:
251016
Hom.:
91487
AF XY:
0.850
AC XY:
115309
AN XY:
135662
show subpopulations
Gnomad AFR exome
AF:
0.943
Gnomad AMR exome
AF:
0.766
Gnomad ASJ exome
AF:
0.883
Gnomad EAS exome
AF:
0.912
Gnomad SAS exome
AF:
0.804
Gnomad FIN exome
AF:
0.877
Gnomad NFE exome
AF:
0.860
Gnomad OTH exome
AF:
0.849
GnomAD4 exome
AF:
0.855
AC:
1245979
AN:
1456548
Hom.:
533859
Cov.:
33
AF XY:
0.854
AC XY:
619255
AN XY:
724960
show subpopulations
Gnomad4 AFR exome
AF:
0.947
Gnomad4 AMR exome
AF:
0.770
Gnomad4 ASJ exome
AF:
0.880
Gnomad4 EAS exome
AF:
0.902
Gnomad4 SAS exome
AF:
0.802
Gnomad4 FIN exome
AF:
0.880
Gnomad4 NFE exome
AF:
0.857
Gnomad4 OTH exome
AF:
0.859
GnomAD4 genome
AF:
0.879
AC:
133729
AN:
152184
Hom.:
58941
Cov.:
32
AF XY:
0.877
AC XY:
65279
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.944
Gnomad4 AMR
AF:
0.798
Gnomad4 ASJ
AF:
0.891
Gnomad4 EAS
AF:
0.913
Gnomad4 SAS
AF:
0.810
Gnomad4 FIN
AF:
0.884
Gnomad4 NFE
AF:
0.859
Gnomad4 OTH
AF:
0.862
Alfa
AF:
0.863
Hom.:
92499
Bravo
AF:
0.876
Asia WGS
AF:
0.853
AC:
2967
AN:
3478
EpiCase
AF:
0.856
EpiControl
AF:
0.860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
12
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs2156634; hg19: chr11-120776001; API