Variant chr11-120862007-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014619.5(GRIK4):c.793A>G(p.Ile265Val) variant causes a missense change. The variant allele was found at a frequency of 0.00174 in 1,613,988 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 23 hom. )

Consequence

GRIK4
NM_014619.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.10

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068692267).

BP6

Variant 11-120862007-A-G is Benign according to our data. Variant chr11-120862007-A-G is described in ClinVar as [Benign]. Clinvar id is 768491.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00926 (1411/152350) while in subpopulation AFR AF= 0.0316 (1315/41582). AF 95% confidence interval is 0.0302. There are 20 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1411 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5 linkuse as main transcript	c.793A>G	p.Ile265Val	missense_variant	9/21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8 linkuse as main transcript	c.793A>G	p.Ile265Val	missense_variant	9/21	2	NM_014619.5	ENSP00000435648	P1

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1410

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00231

AC:

581

AN:

251448

Hom.:

AF XY:

0.00177

AC XY:

240

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.0000992

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:

0.00114

GnomAD4 exome

AF:

0.000956

AC:

1398

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

581

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00926

AC:

1411

AN:

152350

Hom.:

Cov.:

AF XY:

0.00872

AC XY:

650

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.0108

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00274

AC:

333

Asia WGS

AF:

0.00173

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

0.046

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;.;D

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.50

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.075

T;.;T

Sift4G

Benign

0.28

T;.;T

Polyphen

0.0050

B;B;B

Vest4

0.35

MVP

0.69

MPC

0.43

ClinPred

0.024

GERP RS

5.8

Varity_R

0.13

gMVP

0.65

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