chr11-120919143-T-C

Position:

• chr11-120919143-T-C

Variant summary

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

The NM_014619.5(GRIK4):​c.1476+13650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,064 control chromosomes in the GnomAD database, including 26,259 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 0.57 (26259 hom., cov: 32)
• Consequence: GRIK4 NM_014619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIK4	NM_014619.5	c.1476+13650T>C		intron_variant		ENST00000527524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIK4	ENST00000527524.8	c.1476+13650T>C		intron_variant		2	NM_014619.5	P1
GRIK4	ENST00000438375.2	c.1476+13650T>C		intron_variant		1		P1
GRIK4	ENST00000533291.5	n.1874+13650T>C		intron_variant, non_coding_transcript_variant		1
GRIK4	ENST00000638419.1	c.1476+13650T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86597 AN: 151946 Hom.: 26217 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.570 AC: 86703 AN: 152064 Hom.: 26259 Cov.: 32 AF XY: 0.567 AC XY: 42108 AN XY: 74320

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.550

Alfa AF: 0.486 Hom.: 36614

Bravo AF: 0.581

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.71

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: rs949295; hg19: chr11-120789852;