rs2156634

Positions:

• chr11-120905292-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014619.5(GRIK4):​c.1275G>A​(p.Glu425=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

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]

ACMG classification

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/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.1275G>A	p.Glu425=	splice_region_variant, synonymous_variant	13/21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.1275G>A	p.Glu425=	splice_region_variant, synonymous_variant	13/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2	c.1275G>A	p.Glu425=	splice_region_variant, synonymous_variant	12/20	1		ENSP00000404063	P1
GRIK4	ENST00000533291.5	n.1673G>A		splice_region_variant, non_coding_transcript_exon_variant	13/18	1
GRIK4	ENST00000638419.1	c.1275G>A	p.Glu425=	splice_region_variant, synonymous_variant	13/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133637 AN: 152066 Hom.: 58896 Cov.: 32

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

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

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

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

Other links and lift over

dbSNP: rs2156634; hg19: chr11-120776001;