Variant rs2240157 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138690.3(GRIN3B):c.1240T>C(p.Trp414Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,607,864 control chromosomes in the GnomAD database, including 403,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.72 ( 39300 hom., cov: 34)

Exomes 𝑓: 0.70 ( 364026 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

GRIN3B (HGNC:16768): (glutamate ionotropic receptor NMDA type subunit 3B) The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

GRIN3B links:

GRIN3B (HGNC:):

GRIN3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9714284E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.1240T>C	p.Trp414Arg	missense_variant	3/9	ENST00000234389.3	NP_619635.1	O60391Q5F0I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3 linkuse as main transcript	c.1240T>C	p.Trp414Arg	missense_variant	3/9	1	NM_138690.3	ENSP00000234389.3		O60391
GRIN3B	ENST00000588335.1 linkuse as main transcript	n.51-61T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108787

AN:

151976

Hom.:

39250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.789

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.803

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.758

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.738

GnomAD3 exomes

AF:

0.680

AC:

165352

AN:

243026

Hom.:

57543

AF XY:

0.688

AC XY:

91147

AN XY:

132394

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.798

Gnomad EAS exome

AF:

0.492

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.700

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.705

AC:

1026228

AN:

1455768

Hom.:

364026

Cov.:

AF XY:

0.707

AC XY:

511438

AN XY:

723454

show subpopulations

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.799

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.705

Gnomad4 NFE exome

AF:

0.709

Gnomad4 OTH exome

AF:

0.710

GnomAD4 genome

AF:

0.716

AC:

108891

AN:

152096

Hom.:

39300

Cov.:

AF XY:

0.713

AC XY:

52991

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.790

Gnomad4 AMR

AF:

0.593

Gnomad4 ASJ

AF:

0.803

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.760

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.705

Hom.:

36378

Bravo

AF:

0.709

TwinsUK

AF:

0.705

AC:

2613

ALSPAC

AF:

0.715

AC:

2755

ESP6500AA

AF:

0.786

AC:

3447

ESP6500EA

AF:

0.712

AC:

6108

ExAC

AF:

0.686

AC:

82899

Asia WGS

AF:

0.658

AC:

2292

AN:

3478

EpiCase

AF:

0.720

EpiControl

AF:

0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.1

DANN

Benign

0.44

DEOGEN2

Benign

0.021

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.049

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.6

PrimateAI

Uncertain

0.71

PROVEAN

Benign

3.2

REVEL

Benign

0.067

Sift

Benign

0.39

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.022

MutPred

0.28

Gain of disorder (P = 0.0016);

MPC

0.20

ClinPred

0.012

GERP RS

3.4

Varity_R

0.043

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over