11-120714142-T-C

Variant names:

• chr11-120714142-T-C
• rs3133855
• NM_014619.5:c.82+53742T>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.82+53742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,152 control chromosomes in the GnomAD database, including 30,239 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 0.63 (30239 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.82+53742T>C		intron_variant	Intron 3 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.82+53742T>C		intron_variant	Intron 3 of 20	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95531 AN: 152034 Hom.: 30223 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.628 AC: 95592 AN: 152152 Hom.: 30239 Cov.: 33 AF XY: 0.627 AC XY: 46638 AN XY: 74384

African (AFR) AF: 0.562 AC: 23343 AN: 41518

American (AMR) AF: 0.606 AC: 9263 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2112 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3030 AN: 5168

South Asian (SAS) AF: 0.766 AC: 3691 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6480 AN: 10578

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45488 AN: 67990

Other (OTH) AF: 0.656 AC: 1385 AN: 2110

Alfa AF: 0.654 Hom.: 51611

Bravo AF: 0.623

Asia WGS AF: 0.675 AC: 2344 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	0.89
DANN	Benign	0.47
PhyloP100		-0.81
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: rs3133855; hg19: chr11-120584851;