rs948028

Variant names:

• chr11-120773738-A-C
• rs948028
• NM_014619.5:c.83-28955A>C

Variant summary

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

The NM_014619.5(GRIK4):​c.83-28955A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,070 control chromosomes in the GnomAD database, including 11,191 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 0.32 (11191 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.83-28955A>C		intron_variant	Intron 3 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.83-28955A>C		intron_variant	Intron 3 of 20	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48547 AN: 151952 Hom.: 11145 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.320 AC: 48651 AN: 152070 Hom.: 11191 Cov.: 33 AF XY: 0.317 AC XY: 23587 AN XY: 74336

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.283

Alfa AF: 0.190 Hom.: 7198

Bravo AF: 0.348

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.75

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: rs948028; hg19: chr11-120644447;