Variant 11-120831976-C-T details in Genebe, Genetics Data Aggregator

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

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]

GRIK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

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

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BS2

High AC in GnomAd4 at 185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5 linkuse as main transcript	c.636C>T	p.Thr212=	synonymous_variant	7/21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GRIK4	ENST00000527524.8 linkuse as main transcript	c.636C>T	p.Thr212=	synonymous_variant	7/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2 linkuse as main transcript	c.636C>T	p.Thr212=	synonymous_variant	6/20	1		ENSP00000404063	P1
GRIK4	ENST00000533291.5 linkuse as main transcript	n.1034C>T		non_coding_transcript_exon_variant	7/18	1
GRIK4	ENST00000638419.1 linkuse as main transcript	c.636C>T	p.Thr212=	synonymous_variant	7/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152118

Hom.:

Cov.:

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.:

AF XY:

0.000721

AC XY:

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.:

Cov.:

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

AF:

0.00122

AC:

185

AN:

152118

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

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.:

Bravo

AF:

0.000778

Asia WGS

AF:

0.000289

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over