rs2284425

Variant summary

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

The NM_000834.5(GRIN2B):​c.411+29713C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,180 control chromosomes in the GnomAD database, including 4,485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4485 hom., cov: 32)

Consequence

GRIN2B
NM_000834.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.650
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]

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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 (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2BNM_000834.5 linkuse as main transcriptc.411+29713C>A intron_variant ENST00000609686.4
LOC105369667XR_931370.4 linkuse as main transcriptn.66-579G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2BENST00000609686.4 linkuse as main transcriptc.411+29713C>A intron_variant 1 NM_000834.5 P1
GRIN2BENST00000630791.2 linkuse as main transcriptc.411+29713C>A intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.231
AC:
35060
AN:
152060
Hom.:
4473
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.131
Gnomad AMI
AF:
0.103
Gnomad AMR
AF:
0.226
Gnomad ASJ
AF:
0.290
Gnomad EAS
AF:
0.284
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.266
Gnomad NFE
AF:
0.285
Gnomad OTH
AF:
0.233
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.231
AC:
35086
AN:
152180
Hom.:
4485
Cov.:
32
AF XY:
0.228
AC XY:
16948
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.131
Gnomad4 AMR
AF:
0.227
Gnomad4 ASJ
AF:
0.290
Gnomad4 EAS
AF:
0.285
Gnomad4 SAS
AF:
0.312
Gnomad4 FIN
AF:
0.205
Gnomad4 NFE
AF:
0.285
Gnomad4 OTH
AF:
0.233
Alfa
AF:
0.276
Hom.:
7944
Bravo
AF:
0.227
Asia WGS
AF:
0.317
AC:
1103
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
6.2
DANN
Benign
0.64

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.

Other links and lift over

dbSNP: rs2284425; hg19: chr12-13989019; API