Menu
GeneBe

11-120831976-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014619.5(GRIK4):c.636C>T(p.Thr212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

GRIK4
NM_014619.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-120831976-C-T is Benign according to our data. Variant chr11-120831976-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720353.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=-2.31 with no splicing effect.
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 185 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIK4NM_014619.5 linkuse as main transcriptc.636C>T p.Thr212= synonymous_variant 7/21 ENST00000527524.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIK4ENST00000527524.8 linkuse as main transcriptc.636C>T p.Thr212= synonymous_variant 7/212 NM_014619.5 P1
GRIK4ENST00000438375.2 linkuse as main transcriptc.636C>T p.Thr212= synonymous_variant 6/201 P1
GRIK4ENST00000533291.5 linkuse as main transcriptn.1034C>T non_coding_transcript_exon_variant 7/181
GRIK4ENST00000638419.1 linkuse as main transcriptc.636C>T p.Thr212= synonymous_variant 7/215 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00122
AC:
185
AN:
152118
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00235
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000768
AC:
193
AN:
251374
Hom.:
1
AF XY:
0.000721
AC XY:
98
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.00143
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00106
AC:
1549
AN:
1461654
Hom.:
1
Cov.:
32
AF XY:
0.00105
AC XY:
761
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000300
Gnomad4 NFE exome
AF:
0.00128
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00122
AC:
185
AN:
152118
Hom.:
0
Cov.:
31
AF XY:
0.00109
AC XY:
81
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.000362
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00235
Gnomad4 OTH
AF:
0.000957
Alfa
AF:
0.00138
Hom.:
0
Bravo
AF:
0.000778
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00202
EpiControl
AF:
0.000948

ClinVar

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

Submissions by phenotype

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

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
6.0
Dann
Benign
0.90

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: rs148308915; hg19: chr11-120702685; COSMIC: COSV70803882; API