chr12-13563020-G-A

Position:

chr12-13563020-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000834.5(GRIN2B):c.4218C>T(p.Phe1406=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0367 in 1,613,930 control chromosomes in the GnomAD database, including 1,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 98 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1240 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 4.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 12-13563020-G-A is Benign according to our data. Variant chr12-13563020-G-A is described in ClinVar as [Benign]. Clinvar id is 98431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-13563020-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0798 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.4218C>T	p.Phe1406=	synonymous_variant	14/14	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1 linkuse as main transcript	c.4218C>T	p.Phe1406=	synonymous_variant	15/15		NP_001400921.1
GRIN2B	XM_005253351.3 linkuse as main transcript	c.2004C>T	p.Phe668=	synonymous_variant	4/4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4 linkuse as main transcript	c.4218C>T	p.Phe1406=	synonymous_variant	14/14	1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000637214.1 linkuse as main transcript	c.69+45583C>T		intron_variant		5		ENSP00000489997

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4328

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00697

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0861

Gnomad SAS

AF:

0.0760

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0400

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.0367

AC:

9228

AN:

251330

Hom.:

247

AF XY:

0.0389

AC XY:

5291

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00635

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.0874

Gnomad SAS exome

AF:

0.0702

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0376

AC:

54901

AN:

1461600

Hom.:

1240

Cov.:

AF XY:

0.0387

AC XY:

28108

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00603

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.0689

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.0371

Gnomad4 OTH exome

AF:

0.0394

GnomAD4 genome

AF:

0.0284

AC:

4326

AN:

152330

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2085

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00695

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.0865

Gnomad4 SAS

AF:

0.0759

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0400

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0720

AC:

249

AN:

3478

EpiCase

AF:

0.0356

EpiControl

AF:

0.0333

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Psychiatry Genetics Yale University	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 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

-0.46

CADD

Benign

DANN

Benign

0.73

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