rs3026160

Positions:

Variant summary

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

The NM_000834.5(GRIN2B):c.2514C>T(p.Cys838=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,670 control chromosomes in the GnomAD database, including 12,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 689 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11809 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.648

Variant links:

Genes affected

GRIN2B (HGNC:4586): (glutamate ionotropic receptor NMDA type subunit 2B) This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

GRIN2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-13567109-G-A is Benign according to our data. Variant chr12-13567109-G-A is described in ClinVar as [Benign]. Clinvar id is 129202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-13567109-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.648 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GRIN2B	NM_000834.5 linkuse as main transcript	c.2514C>T	p.Cys838=	synonymous_variant	13/14	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1 linkuse as main transcript	c.2514C>T	p.Cys838=	synonymous_variant	14/15		NP_001400921.1
GRIN2B	XM_005253351.3 linkuse as main transcript	c.300C>T	p.Cys100=	synonymous_variant	3/4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GRIN2B	ENST00000609686.4 linkuse as main transcript	c.2514C>T	p.Cys838=	synonymous_variant	13/14	1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000637214.1 linkuse as main transcript	c.69+41494C>T		intron_variant		5		ENSP00000489997
GRIN2B	ENST00000628166.2 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0807

AC:

12285

AN:

152160

Hom.:

689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0558

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0890

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0685

GnomAD3 exomes

AF:

0.0858

AC:

21581

AN:

251480

Hom.:

1212

AF XY:

0.0892

AC XY:

12128

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0416

Gnomad ASJ exome

AF:

0.0727

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0667

Gnomad FIN exome

AF:

0.0860

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.0971

GnomAD4 exome

AF:

0.120

AC:

174886

AN:

1461392

Hom.:

11809

Cov.:

AF XY:

0.118

AC XY:

85758

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.0443

Gnomad4 ASJ exome

AF:

0.0757

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0686

Gnomad4 FIN exome

AF:

0.0893

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0807

AC:

12285

AN:

152278

Hom.:

689

Cov.:

AF XY:

0.0766

AC XY:

5702

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0557

Gnomad4 ASJ

AF:

0.0786

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0633

Gnomad4 FIN

AF:

0.0890

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.0678

Alfa

AF:

0.111

Hom.:

1759

Bravo

AF:

0.0764

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.122

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 21, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.7

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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