11-120987701-G-A

Variant names:

• chr11-120987701-G-A
• rs2282586
• NM_014619.5:c.*1441G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014619.5. 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.*1441G>A		3_prime_UTR	Exon 21 of 21	NP_055434.2
	GRIK4	NM_001282470.3		c.*1441G>A		3_prime_UTR	Exon 20 of 20	NP_001269399.1
	GRIK4	NM_001440402.1		c.*1441G>A		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.*1441G>A		3_prime_UTR	Exon 21 of 21	ENSP00000435648.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 2 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.353 AC: 12 AN: 34

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.199 AC: 8258 AN: 41444

American (AMR) AF: 0.443 AC: 6768 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1912 AN: 5154

South Asian (SAS) AF: 0.378 AC: 1817 AN: 4812

European-Finnish (FIN) AF: 0.415 AC: 4380 AN: 10556

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27396 AN: 67934

Other (OTH) AF: 0.374 AC: 790 AN: 2110

Alfa AF: 0.393 Hom.: 20476

Bravo AF: 0.350

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2282586; hg19: chr11-120858410;