rs2276319

Positions:

• chr11-120967112-G-A
• chr11-120967112-G-T

Variant summary

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

The NM_014619.5(GRIK4):​c.2267-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,463,536 control chromosomes in the GnomAD database, including 243,071 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 (22852 hom., cov: 32)
  • Exomes 𝑓: 0.57 (220219 hom.)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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 = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK4	NM_014619.5	c.2267-83G>A		intron_variant		ENST00000527524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK4	ENST00000527524.8	c.2267-83G>A		intron_variant		2	NM_014619.5	P1
GRIK4	ENST00000438375.2	c.2267-83G>A		intron_variant		1		P1
GRIK4	ENST00000638419.1	c.2267-83G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82350 AN: 151990 Hom.: 22842 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.575 AC: 753843 AN: 1311428 Hom.: 220219 AF XY: 0.571 AC XY: 369739 AN XY: 647278

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.542 AC: 82389 AN: 152108 Hom.: 22852 Cov.: 32 AF XY: 0.540 AC XY: 40163 AN XY: 74364

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.579

Alfa AF: 0.586 Hom.: 34436

Bravo AF: 0.541

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.82

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: rs2276319; hg19: chr11-120837821; COSMIC: COSV70802361; COSMIC: COSV70802361;