chr11-120987701-G-A

Position:

• chr11-120987701-G-A

Variant summary

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

The NM_014619.5(GRIK4):​c.*1441G>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 0.35 in 152,004 control chromosomes in the GnomAD database, including 10,025 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 0.35 (10024 hom., cov: 32)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: GRIK4 NM_014619.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.*1441G>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.*1441G>A		3_prime_UTR_variant	21/21	2	NM_014619.5	ENSP00000435648	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53200 AN: 151844 Hom.: 10018 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.333 AC: 14 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 12 AN XY: 30

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.353

GnomAD4 genome AF: 0.350 AC: 53234 AN: 151962 Hom.: 10024 Cov.: 32 AF XY: 0.353 AC XY: 26217 AN XY: 74270

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.374

Alfa AF: 0.398 Hom.: 16514

Bravo AF: 0.350

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2282586; hg19: chr11-120858410;