11-120649920-T-C

Variant names:

• chr11-120649920-T-C
• rs4245040
• NM_014619.5:c.-158-3765T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014619.5(GRIK4):​c.-158-3765T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,208 control chromosomes in the GnomAD database, including 43,692 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 0.75 (43692 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.-158-3765T>C		intron_variant	Intron 1 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.-158-3765T>C		intron_variant	Intron 1 of 20	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114249 AN: 152090 Hom.: 43633 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.751 AC: 114367 AN: 152208 Hom.: 43692 Cov.: 33 AF XY: 0.750 AC XY: 55791 AN XY: 74408

African (AFR) AF: 0.909 AC: 37786 AN: 41574

American (AMR) AF: 0.692 AC: 10572 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2392 AN: 3470

East Asian (EAS) AF: 0.776 AC: 4020 AN: 5182

South Asian (SAS) AF: 0.695 AC: 3351 AN: 4824

European-Finnish (FIN) AF: 0.662 AC: 7007 AN: 10584

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46946 AN: 67980

Other (OTH) AF: 0.709 AC: 1498 AN: 2114

Alfa AF: 0.704 Hom.: 4829

Bravo AF: 0.761

Asia WGS AF: 0.730 AC: 2539 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	0.022
DANN	Benign	0.37
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4245040; hg19: chr11-120520629;