11-120818410-A-C

Variant names:

• chr11-120818410-A-C
• rs4935752
• NM_014619.5:c.346-1345A>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.346-1345A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,144 control chromosomes in the GnomAD database, including 7,412 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 0.29 (7412 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• 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]

ENSG00000306735 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 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.346-1345A>C		intron	N/A	NP_055434.2
	GRIK4	NM_001282470.3		c.346-1345A>C		intron	N/A	NP_001269399.1
	GRIK4	NM_001440402.1		c.346-1345A>C		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.346-1345A>C		intron	N/A	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.346-1345A>C		intron	N/A	ENSP00000404063.2
	GRIK4	ENST00000533291.5	TSL:1	n.744-1345A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44400 AN: 152026 Hom.: 7420 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.292 AC: 44397 AN: 152144 Hom.: 7412 Cov.: 33 AF XY: 0.293 AC XY: 21813 AN XY: 74384

African (AFR) AF: 0.125 AC: 5175 AN: 41524

American (AMR) AF: 0.253 AC: 3867 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5164

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4826

European-Finnish (FIN) AF: 0.414 AC: 4383 AN: 10592

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24797 AN: 67968

Other (OTH) AF: 0.314 AC: 664 AN: 2112

Alfa AF: 0.341 Hom.: 15688

Bravo AF: 0.274

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-0.65
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: rs4935752; hg19: chr11-120689119;