rs4936554

Positions:

• chr11-120820576-C-T

Variant summary

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

The NM_014619.5(GRIK4):​c.511+656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,180 control chromosomes in the GnomAD database, including 3,662 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 0.19 (3662 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK4	NM_014619.5	c.511+656C>T		intron_variant		ENST00000527524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK4	ENST00000527524.8	c.511+656C>T		intron_variant		2	NM_014619.5	P1
GRIK4	ENST00000438375.2	c.511+656C>T		intron_variant		1		P1
GRIK4	ENST00000533291.5	n.909+656C>T		intron_variant, non_coding_transcript_variant		1
GRIK4	ENST00000638419.1	c.511+656C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29634 AN: 152062 Hom.: 3653 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.195 AC: 29648 AN: 152180 Hom.: 3662 Cov.: 33 AF XY: 0.197 AC XY: 14686 AN XY: 74400

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.209

Alfa AF: 0.223 Hom.: 3109

Bravo AF: 0.205

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.56

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: rs4936554; hg19: chr11-120691285;