Variant chr1-36841856-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000831.4(GRIK3):c.1410A>G(p.Leu470=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,614,132 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 113 hom. )

Consequence

GRIK3
NM_000831.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

GRIK3 (HGNC:4581): (glutamate ionotropic receptor kainate type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. It is not certain if the subunit encoded by this gene is subject to RNA editing as the other 2 family members (GRIK1 and GRIK2). A Ser310Ala polymorphism has been associated with schizophrenia, and there are conflicting reports of its association with the pathogenesis of delirium tremens in alcoholics. [provided by RefSeq, Jul 2008]

GRIK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-36841856-T-C is Benign according to our data. Variant chr1-36841856-T-C is described in ClinVar as [Benign]. Clinvar id is 717890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIK3	NM_000831.4 linkuse as main transcript	c.1410A>G	p.Leu470=	synonymous_variant	10/16	ENST00000373091.8	NP_000822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIK3	ENST00000373091.8 linkuse as main transcript	c.1410A>G	p.Leu470=	synonymous_variant	10/16	1	NM_000831.4	ENSP00000362183	P1	Q13003-1
GRIK3	ENST00000373093.4 linkuse as main transcript	c.1410A>G	p.Leu470=	synonymous_variant	10/15	1		ENSP00000362185		Q13003-2

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

541

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0845

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00882

AC:

2219

AN:

251494

Hom.:

AF XY:

0.00803

AC XY:

1091

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00963

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0961

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00269

AC:

3928

AN:

1461860

Hom.:

113

Cov.:

AF XY:

0.00260

AC XY:

1894

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00852

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152272

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0843

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.000754

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

-0.84

CADD

Benign

0.26

DANN

Benign

0.39

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