NM_014619.5:c.2267-83G>A

Variant names:

• chr11-120967112-G-A
• rs2276319
• NM_014619.5:c.2267-83G>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.2267-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,463,536 control chromosomes in the GnomAD database, including 243,071 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 0.54 (22852 hom., cov: 32)
  • Exomes 𝑓: 0.57 (220219 hom.)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.588 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.2267-83G>A		intron	N/A	NP_055434.2
	GRIK4	NM_001282470.3		c.2267-83G>A		intron	N/A	NP_001269399.1
	GRIK4	NM_001440402.1		c.2267-83G>A		intron	N/A	NP_001427331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.2267-83G>A		intron	N/A	ENSP00000435648.2
	GRIK4	ENST00000438375.2	TSL:1	c.2267-83G>A		intron	N/A	ENSP00000404063.2
	GRIK4	ENST00000638419.1	TSL:5	c.2267-83G>A		intron	N/A	ENSP00000492086.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82350 AN: 151990 Hom.: 22842 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.575 AC: 753843 AN: 1311428 Hom.: 220219 AF XY: 0.571 AC XY: 369739 AN XY: 647278

African (AFR) AF: 0.439 AC: 12982 AN: 29546

American (AMR) AF: 0.576 AC: 20049 AN: 34796

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 13096 AN: 20458

East Asian (EAS) AF: 0.333 AC: 12447 AN: 37410

South Asian (SAS) AF: 0.436 AC: 30644 AN: 70212

European-Finnish (FIN) AF: 0.593 AC: 29453 AN: 49658

Middle Eastern (MID) AF: 0.654 AC: 3427 AN: 5238

European-Non Finnish (NFE) AF: 0.595 AC: 601142 AN: 1009676

Other (OTH) AF: 0.562 AC: 30603 AN: 54434

GnomAD4 genome AF: 0.542 AC: 82389 AN: 152108 Hom.: 22852 Cov.: 32 AF XY: 0.540 AC XY: 40163 AN XY: 74364

African (AFR) AF: 0.452 AC: 18738 AN: 41496

American (AMR) AF: 0.598 AC: 9146 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2201 AN: 3472

East Asian (EAS) AF: 0.355 AC: 1827 AN: 5150

South Asian (SAS) AF: 0.428 AC: 2063 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6305 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40093 AN: 67984

Other (OTH) AF: 0.579 AC: 1222 AN: 2110

Alfa AF: 0.582 Hom.: 42595

Bravo AF: 0.541

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		1.6
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: rs2276319; hg19: chr11-120837821; COSMIC: COSV70802361; COSMIC: COSV70802361;