rs513548

Variant names:

• chr11-120977108-C-T
• rs513548
• NM_014619.5:c.2396-4998C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014619.5(GRIK4):​c.2396-4998C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,098 control chromosomes in the GnomAD database, including 43,544 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 0.75 (43544 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AMR) 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.2396-4998C>T		intron	N/A	NP_055434.2
	GRIK4	NM_001282470.3		c.2396-4998C>T		intron	N/A	NP_001269399.1
	GRIK4	NM_001440402.1		c.2396-4998C>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.2396-4998C>T		intron	N/A	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.2396-4998C>T		intron	N/A	ENSP00000404063.2
	GRIK4	ENST00000638419.1	TSL:5	c.2396-4998C>T		intron	N/A	ENSP00000492086.1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114741 AN: 151978 Hom.: 43514 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.755 AC: 114832 AN: 152098 Hom.: 43544 Cov.: 32 AF XY: 0.753 AC XY: 56016 AN XY: 74358

African (AFR) AF: 0.727 AC: 30172 AN: 41480

American (AMR) AF: 0.805 AC: 12307 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2743 AN: 3468

East Asian (EAS) AF: 0.624 AC: 3227 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3255 AN: 4820

European-Finnish (FIN) AF: 0.745 AC: 7879 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52668 AN: 67988

Other (OTH) AF: 0.772 AC: 1624 AN: 2104

Alfa AF: 0.763 Hom.: 22662

Bravo AF: 0.759

Asia WGS AF: 0.628 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.8
DANN	Benign	0.86
PhyloP100		0.31
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: rs513548; hg19: chr11-120847817;