NM_014619.5:c.744+12441A>G

Variant names:

• chr11-120849285-A-G
• rs11218030
• NM_014619.5:c.744+12441A>G

Variant summary

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

The NM_014619.5(GRIK4):​c.744+12441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,210 control chromosomes in the GnomAD database, including 2,726 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 0.16 (2726 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.744+12441A>G		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.744+12441A>G		intron_variant	Intron 8 of 20	2	NM_014619.5	ENSP00000435648.2
GRIK4	ENST00000438375.2	c.744+12441A>G		intron_variant	Intron 7 of 19	1		ENSP00000404063.2
GRIK4	ENST00000533291.5	n.1142+12441A>G		intron_variant	Intron 8 of 17	1
GRIK4	ENST00000638419.1	c.744+12441A>G		intron_variant	Intron 8 of 20	5		ENSP00000492086.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24535 AN: 152092 Hom.: 2724 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.161 AC: 24539 AN: 152210 Hom.: 2726 Cov.: 32 AF XY: 0.163 AC XY: 12149 AN XY: 74418

African (AFR) AF: 0.0480 AC: 1995 AN: 41558

American (AMR) AF: 0.319 AC: 4872 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1696 AN: 5170

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4808

European-Finnish (FIN) AF: 0.124 AC: 1318 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12432 AN: 67998

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.187 Hom.: 2631

Bravo AF: 0.174

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.69
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: rs11218030; hg19: chr11-120719994;