rs7104543

Variant names:

• chr11-120853412-A-G
• rs7104543
• NM_014619.5:c.745-8547A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014619.5(GRIK4):​c.745-8547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,026 control chromosomes in the GnomAD database, including 19,728 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 0.50 (19728 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.745-8547A>G		intron_variant	Intron 8 of 20	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.745-8547A>G		intron_variant	Intron 8 of 20	2	NM_014619.5	ENSP00000435648.2
GRIK4	ENST00000438375.2	c.745-8547A>G		intron_variant	Intron 7 of 19	1		ENSP00000404063.2
GRIK4	ENST00000533291.5	n.1143-8547A>G		intron_variant	Intron 8 of 17	1
GRIK4	ENST00000638419.1	c.745-8547A>G		intron_variant	Intron 8 of 20	5		ENSP00000492086.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75629 AN: 151908 Hom.: 19692 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75714 AN: 152026 Hom.: 19728 Cov.: 32 AF XY: 0.497 AC XY: 36984 AN XY: 74340

African (AFR) AF: 0.646 AC: 26768 AN: 41446

American (AMR) AF: 0.570 AC: 8715 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1697 AN: 5174

South Asian (SAS) AF: 0.372 AC: 1789 AN: 4812

European-Finnish (FIN) AF: 0.437 AC: 4610 AN: 10558

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28979 AN: 67966

Other (OTH) AF: 0.477 AC: 1008 AN: 2112

Alfa AF: 0.456 Hom.: 46553

Bravo AF: 0.519

Asia WGS AF: 0.360 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.43
PhyloP100		-1.3
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: rs7104543; hg19: chr11-120724121;