rs12800734

Positions:

• chr11-120966045-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014619.5(GRIK4):​c.2267-1150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,990 control chromosomes in the GnomAD database, including 22,703 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 0.54 (22703 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK4	NM_014619.5	c.2267-1150G>A		intron_variant		ENST00000527524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK4	ENST00000527524.8	c.2267-1150G>A		intron_variant		2	NM_014619.5	P1
GRIK4	ENST00000438375.2	c.2267-1150G>A		intron_variant		1		P1
GRIK4	ENST00000638419.1	c.2267-1150G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82070 AN: 151870 Hom.: 22693 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.540 AC: 82109 AN: 151990 Hom.: 22703 Cov.: 32 AF XY: 0.539 AC XY: 40019 AN XY: 74298

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.577

Alfa AF: 0.583 Hom.: 22254

Bravo AF: 0.540

Asia WGS AF: 0.377 AC: 1312 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.65

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: rs12800734; hg19: chr11-120836754;