chr11-120614101-A-G

Position:

• chr11-120614101-A-G

Variant summary

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

The NM_014619.5(GRIK4):​c.-158-39584A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,050 control chromosomes in the GnomAD database, including 7,279 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 0.30 (7279 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.-158-39584A>G		intron_variant		ENST00000527524.8	NP_055434.2
GRIK4	NM_001282470.3	c.-50-46168A>G		intron_variant			NP_001269399.1
GRIK4	NM_001282473.3	c.-158-39584A>G		intron_variant			NP_001269402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.-158-39584A>G		intron_variant		2	NM_014619.5	ENSP00000435648	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45285 AN: 151934 Hom.: 7277 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.298 AC: 45322 AN: 152050 Hom.: 7279 Cov.: 32 AF XY: 0.294 AC XY: 21822 AN XY: 74306

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.284

Alfa AF: 0.314 Hom.: 926

Bravo AF: 0.285

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.22

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: rs1317814; hg19: chr11-120484810;