11-120792654-T-C

Variant names:

• chr11-120792654-T-C
• rs1954787
• NM_014619.5:c.83-10039T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014619.5(GRIK4):​c.83-10039T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,946 control chromosomes in the GnomAD database, including 18,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18642 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30
• Publications: 55 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-120792654-T-C is Benign according to our data. Variant chr11-120792654-T-C is described in ClinVar as [Benign]. Clinvar id is 225967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.83-10039T>C		intron_variant	Intron 3 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.83-10039T>C		intron_variant	Intron 3 of 20	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69554 AN: 151828 Hom.: 18635 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.458 AC: 69573 AN: 151946 Hom.: 18642 Cov.: 32 AF XY: 0.459 AC XY: 34060 AN XY: 74240

African (AFR) AF: 0.175 AC: 7261 AN: 41446

American (AMR) AF: 0.596 AC: 9099 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1891 AN: 3462

East Asian (EAS) AF: 0.845 AC: 4365 AN: 5168

South Asian (SAS) AF: 0.574 AC: 2759 AN: 4806

European-Finnish (FIN) AF: 0.488 AC: 5141 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37437 AN: 67950

Other (OTH) AF: 0.492 AC: 1038 AN: 2110

Alfa AF: 0.522 Hom.: 72432

Bravo AF: 0.457

Asia WGS AF: 0.678 AC: 2355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.63
DANN	Benign	0.73
PhyloP100		-1.3
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: rs1954787; hg19: chr11-120663363;