chr11-120852724-T-G

Variant names:

• chr11-120852724-T-G
• rs4430518
• NM_014619.5:c.745-9235T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_014619.5(GRIK4):​c.745-9235T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,060 control chromosomes in the GnomAD database, including 7,074 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 0.30 (7074 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 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.745-9235T>G		intron	N/A	NP_055434.2
	GRIK4	NM_001282470.3		c.745-9235T>G		intron	N/A	NP_001269399.1
	GRIK4	NM_001440402.1		c.745-9235T>G		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.745-9235T>G		intron	N/A	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.745-9235T>G		intron	N/A	ENSP00000404063.2
	GRIK4	ENST00000533291.5	TSL:1	n.1143-9235T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44947 AN: 151942 Hom.: 7074 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.296 AC: 44977 AN: 152060 Hom.: 7074 Cov.: 32 AF XY: 0.295 AC XY: 21958 AN XY: 74336

African (AFR) AF: 0.347 AC: 14396 AN: 41472

American (AMR) AF: 0.407 AC: 6225 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1780 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4820

European-Finnish (FIN) AF: 0.213 AC: 2252 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17377 AN: 67958

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.266 Hom.: 20785

Bravo AF: 0.315

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.76
PhyloP100		2.2
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: rs4430518; hg19: chr11-120723433;