chr11-120853613-T-A

Variant names:

• chr11-120853613-T-A
• rs11218032
• NM_014619.5:c.745-8346T>A

Variant summary

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

The NM_014619.5(GRIK4):​c.745-8346T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,112 control chromosomes in the GnomAD database, including 8,621 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 0.31 (8621 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.745-8346T>A		intron_variant	Intron 8 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.745-8346T>A		intron_variant	Intron 8 of 20	2	NM_014619.5	ENSP00000435648.2
GRIK4	ENST00000438375.2	c.745-8346T>A		intron_variant	Intron 7 of 19	1		ENSP00000404063.2
GRIK4	ENST00000533291.5	n.1143-8346T>A		intron_variant	Intron 8 of 17	1
GRIK4	ENST00000638419.1	c.745-8346T>A		intron_variant	Intron 8 of 20	5		ENSP00000492086.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46715 AN: 151994 Hom.: 8620 Cov.: 32

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.307 AC: 46722 AN: 152112 Hom.: 8621 Cov.: 32 AF XY: 0.309 AC XY: 22973 AN XY: 74346

African (AFR) AF: 0.0993 AC: 4122 AN: 41526

American (AMR) AF: 0.265 AC: 4049 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2575 AN: 5170

South Asian (SAS) AF: 0.358 AC: 1721 AN: 4812

European-Finnish (FIN) AF: 0.446 AC: 4709 AN: 10562

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26950 AN: 67974

Other (OTH) AF: 0.346 AC: 729 AN: 2106

Alfa AF: 0.351 Hom.: 1301

Bravo AF: 0.286

Asia WGS AF: 0.415 AC: 1441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		0.22
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: rs11218032; hg19: chr11-120724322;