rs4430518

Positions:

• chr11-120852724-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK4	NM_014619.5	c.745-9235T>G		intron_variant		ENST00000527524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK4	ENST00000527524.8	c.745-9235T>G		intron_variant		2	NM_014619.5	P1
GRIK4	ENST00000438375.2	c.745-9235T>G		intron_variant		1		P1
GRIK4	ENST00000533291.5	n.1143-9235T>G		intron_variant, non_coding_transcript_variant		1
GRIK4	ENST00000638419.1	c.745-9235T>G		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.277

Alfa AF: 0.261 Hom.: 9088

Bravo AF: 0.315

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs4430518; hg19: chr11-120723433;