11-120706714-T-C

Position:

• chr11-120706714-T-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+46314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,060 control chromosomes in the GnomAD database, including 6,375 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 0.25 (6375 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.82+46314T>C		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+46314T>C		intron_variant		2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37620 AN: 151942 Hom.: 6353 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.248 AC: 37701 AN: 152060 Hom.: 6375 Cov.: 32 AF XY: 0.245 AC XY: 18243 AN XY: 74338

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.230

Alfa AF: 0.163 Hom.: 3410

Bravo AF: 0.262

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.28

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: rs4567478; hg19: chr11-120577423;