rs10892608

Positions:

• chr11-120679036-G-A
• chr11-120679036-G-C

Variant summary

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

The NM_014619.5(GRIK4):​c.82+18636G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,846 control chromosomes in the GnomAD database, including 16,247 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 0.46 (16247 hom., cov: 30)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.82+18636G>A		intron_variant		ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.82+18636G>A		intron_variant		2	NM_014619.5	ENSP00000435648	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69387 AN: 151726 Hom.: 16224 Cov.: 30

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.457 AC: 69465 AN: 151846 Hom.: 16247 Cov.: 30 AF XY: 0.461 AC XY: 34209 AN XY: 74206

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.462

Alfa AF: 0.480 Hom.: 7549

Bravo AF: 0.454

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.74

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: rs10892608; hg19: chr11-120549745;