11-120829438-G-T

Variant names:

• chr11-120829438-G-T
• rs6589846
• NM_014619.5:c.512-2414G>T

Variant summary

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

The NM_014619.5(GRIK4):​c.512-2414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,978 control chromosomes in the GnomAD database, including 32,933 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 0.65 (32933 hom., cov: 31)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014619.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	NM_014619.5	MANE Select	c.512-2414G>T		intron	N/A	NP_055434.2
	GRIK4	NM_001282470.3		c.512-2414G>T		intron	N/A	NP_001269399.1
	GRIK4	NM_001440402.1		c.512-2414G>T		intron	N/A	NP_001427331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.512-2414G>T		intron	N/A	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.512-2414G>T		intron	N/A	ENSP00000404063.2
	GRIK4	ENST00000533291.5	TSL:1	n.910-2414G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98725 AN: 151860 Hom.: 32887 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.650 AC: 98827 AN: 151978 Hom.: 32933 Cov.: 31 AF XY: 0.647 AC XY: 48076 AN XY: 74254

African (AFR) AF: 0.800 AC: 33175 AN: 41480

American (AMR) AF: 0.515 AC: 7865 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2524 AN: 5148

South Asian (SAS) AF: 0.520 AC: 2501 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6864 AN: 10534

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41373 AN: 67944

Other (OTH) AF: 0.666 AC: 1402 AN: 2106

Alfa AF: 0.620 Hom.: 91876

Bravo AF: 0.647

Asia WGS AF: 0.536 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		0.0050
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: rs6589846; hg19: chr11-120700147;