Variant chr11-120831994-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

GRIK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.906 with no splicing effect.

BS1

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

High AC in GnomAd4 at 1357 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK4	NM_014619.5 linkuse as main transcript	c.654C>T	p.His218=	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.654C>T	p.His218=	synonymous_variant	7/21	2	NM_014619.5	ENSP00000435648	P1
GRIK4	ENST00000438375.2 linkuse as main transcript	c.654C>T	p.His218=	synonymous_variant	6/20	1		ENSP00000404063	P1
GRIK4	ENST00000533291.5 linkuse as main transcript	n.1052C>T		non_coding_transcript_exon_variant	7/18	1
GRIK4	ENST00000638419.1 linkuse as main transcript	c.654C>T	p.His218=	synonymous_variant	7/21	5		ENSP00000492086	P1

Frequencies

GnomAD3 genomes

AF:

0.00892

AC:

1357

AN:

152150

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00891

AC:

1357

AN:

152268

Hom.:

Cov.:

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.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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.

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