rs2156634

Variant names:

• chr11-120905292-G-A
• rs2156634
• NM_014619.5:c.1275G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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
GRIK4	NM_014619.5	c.1275G>A	p.Glu425Glu	splice_region_variant, synonymous_variant	Exon 13 of 21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.1275G>A	p.Glu425Glu	splice_region_variant, synonymous_variant	Exon 13 of 21	2	NM_014619.5	ENSP00000435648.2
GRIK4	ENST00000438375.2	c.1275G>A	p.Glu425Glu	splice_region_variant, synonymous_variant	Exon 12 of 20	1		ENSP00000404063.2
GRIK4	ENST00000533291.5	n.1673G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 13 of 18	1
GRIK4	ENST00000638419.1	c.1275G>A	p.Glu425Glu	splice_region_variant, synonymous_variant	Exon 13 of 21	5		ENSP00000492086.1

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

GnomAD2 exomes AF: 0.852 AC: 213793 AN: 251016 AF XY: 0.850

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 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

African (AFR) AF: 0.947 AC: 31614 AN: 33394

American (AMR) AF: 0.770 AC: 34417 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 22978 AN: 26100

East Asian (EAS) AF: 0.902 AC: 35796 AN: 39670

South Asian (SAS) AF: 0.802 AC: 69069 AN: 86152

European-Finnish (FIN) AF: 0.880 AC: 46840 AN: 53250

Middle Eastern (MID) AF: 0.865 AC: 4970 AN: 5748

European-Non Finnish (NFE) AF: 0.857 AC: 948544 AN: 1107252

Other (OTH) AF: 0.859 AC: 51751 AN: 60262

GnomAD4 genome AF: 0.879 AC: 133729 AN: 152184 Hom.: 58941 Cov.: 32 AF XY: 0.877 AC XY: 65279 AN XY: 74398

African (AFR) AF: 0.944 AC: 39192 AN: 41516

American (AMR) AF: 0.798 AC: 12195 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3092 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4720 AN: 5172

South Asian (SAS) AF: 0.810 AC: 3898 AN: 4812

European-Finnish (FIN) AF: 0.884 AC: 9366 AN: 10600

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58420 AN: 68002

Other (OTH) AF: 0.862 AC: 1822 AN: 2114

Alfa AF: 0.864 Hom.: 122504

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
PhyloP100		3.1
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2156634; hg19: chr11-120776001;