11-120686382-A-T

Position:

• chr11-120686382-A-T

Variant summary

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

The NM_014619.5(GRIK4):​c.82+25982A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,070 control chromosomes in the GnomAD database, including 18,636 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 0.49 (18636 hom., cov: 33)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.82+25982A>T		intron_variant		ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.82+25982A>T		intron_variant		2	NM_014619.5	ENSP00000435648	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74695 AN: 151952 Hom.: 18602 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.492 AC: 74775 AN: 152070 Hom.: 18636 Cov.: 33 AF XY: 0.491 AC XY: 36526 AN XY: 74316

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.475

Alfa AF: 0.471 Hom.: 2142

Bravo AF: 0.493

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	8.0
DANN	Benign	0.37

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: rs10790400; hg19: chr11-120557091;