rs5016722

Positions:

• chr11-120986293-C-A
• chr11-120986293-C-G
• chr11-120986293-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014619.5(GRIK4):​c.*33C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 241,130 control chromosomes in the GnomAD database, including 1 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 0.000021 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00099 (1 hom.)
• Consequence: GRIK4 NM_014619.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS2: High AC in GnomAdExome4 at 145 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.*33C>A		3_prime_UTR_variant	21/21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.*33C>A		3_prime_UTR_variant	21/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2	c.*33C>A		3_prime_UTR_variant	20/20	1		ENSP00000404063	P1
GRIK4	ENST00000638419.1	c.*33C>A		3_prime_UTR_variant	21/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes AF: 0.0000210 AC: 2 AN: 95308 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000252

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00245 AC: 178 AN: 72766 Hom.: 0 AF XY: 0.00240 AC XY: 103 AN XY: 42904

Gnomad AFR exome AF: 0.00321

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00196

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000882

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00335

Gnomad OTH exome AF: 0.00209

GnomAD4 exome AF: 0.000994 AC: 145 AN: 145822 Hom.: 1 Cov.: 0 AF XY: 0.000979 AC XY: 81 AN XY: 82772

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.000922

Gnomad4 ASJ exome AF: 0.000911

Gnomad4 EAS exome AF: 0.000210

Gnomad4 SAS exome AF: 0.000312

Gnomad4 FIN exome AF: 0.000876

Gnomad4 NFE exome AF: 0.00133

Gnomad4 OTH exome AF: 0.000319

GnomAD4 genome AF: 0.0000210 AC: 2 AN: 95308 Hom.: 0 Cov.: 27 AF XY: 0.0000430 AC XY: 2 AN XY: 46540

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.0000252

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00464 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.55
DANN	Benign	0.90

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: rs5016722; hg19: chr11-120857002;