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GeneBe

11-120831994-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_014619.5(GRIK4):c.654C>T(p.His218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,700 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 26 hom., cov: 31)
Exomes 𝑓: 0.00090 ( 21 hom. )

Consequence

GRIK4
NM_014619.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.906
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-120831994-C-T is Benign according to our data. Variant chr11-120831994-C-T is described in ClinVar as [Benign]. Clinvar id is 786216.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.906 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00891 (1357/152268) while in subpopulation AFR AF= 0.0309 (1282/41542). AF 95% confidence interval is 0.0295. There are 26 homozygotes in gnomad4. There are 620 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1357 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIK4NM_014619.5 linkuse as main transcriptc.654C>T p.His218= synonymous_variant 7/21 ENST00000527524.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIK4ENST00000527524.8 linkuse as main transcriptc.654C>T p.His218= synonymous_variant 7/212 NM_014619.5 P1
GRIK4ENST00000438375.2 linkuse as main transcriptc.654C>T p.His218= synonymous_variant 6/201 P1
GRIK4ENST00000533291.5 linkuse as main transcriptn.1052C>T non_coding_transcript_exon_variant 7/181
GRIK4ENST00000638419.1 linkuse as main transcriptc.654C>T p.His218= synonymous_variant 7/215 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00892
AC:
1357
AN:
152150
Hom.:
26
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0310
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00216
AC:
543
AN:
251258
Hom.:
6
AF XY:
0.00150
AC XY:
204
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.0298
Gnomad AMR exome
AF:
0.00142
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000897
AC:
1311
AN:
1461432
Hom.:
21
Cov.:
32
AF XY:
0.000770
AC XY:
560
AN XY:
727018
show subpopulations
Gnomad4 AFR exome
AF:
0.0323
Gnomad4 AMR exome
AF:
0.00152
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00891
AC:
1357
AN:
152268
Hom.:
26
Cov.:
31
AF XY:
0.00833
AC XY:
620
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0309
Gnomad4 AMR
AF:
0.00372
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00360
Hom.:
3
Bravo
AF:
0.0103
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
7.5
Dann
Benign
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112771462; hg19: chr11-120702703; API