11-120986293-C-G

Variant names:

• chr11-120986293-C-G
• rs5016722
• NM_014619.5:c.*33C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000527524.8(GRIK4):​c.*33C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
  • Exomes 𝑓: 0.00023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRIK4 ENST00000527524.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527524.8. 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.*33C>G		3_prime_UTR	Exon 21 of 21	NP_055434.2
	GRIK4	NM_001282470.3		c.*33C>G		3_prime_UTR	Exon 20 of 20	NP_001269399.1
	GRIK4	NM_001440402.1		c.*33C>G		3_prime_UTR	Exon 23 of 23	NP_001427331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.*33C>G		3_prime_UTR	Exon 21 of 21	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.*33C>G		3_prime_UTR	Exon 20 of 20	ENSP00000404063.2
	GRIK4	ENST00000638419.1	TSL:5	c.*33C>G		3_prime_UTR	Exon 21 of 21	ENSP00000492086.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000227 AC: 33 AN: 145654 Hom.: 0 Cov.: 0 AF XY: 0.000266 AC XY: 22 AN XY: 82688

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2624

American (AMR) AF: 0.00 AC: 0 AN: 8676

Ashkenazi Jewish (ASJ) AF: 0.000304 AC: 1 AN: 3292

East Asian (EAS) AF: 0.000422 AC: 2 AN: 4742

South Asian (SAS) AF: 0.000173 AC: 5 AN: 28836

European-Finnish (FIN) AF: 0.000527 AC: 3 AN: 5692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 414

European-Non Finnish (NFE) AF: 0.000223 AC: 19 AN: 85128

Other (OTH) AF: 0.000480 AC: 3 AN: 6250

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.82
DANN	Benign	0.76
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism

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: rs5016722; hg19: chr11-120857002;