12-13634912-T-C

Variant summary

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

The NM_000834.5(GRIN2B):​c.1126-18255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,336 control chromosomes in the GnomAD database, including 217 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 0.035 ( 217 hom., cov: 32)

Consequence

GRIN2B
NM_000834.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37
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=-0.93).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2BNM_000834.5 linkuse as main transcriptc.1126-18255A>G intron_variant ENST00000609686.4
GRIN2BNM_001413992.1 linkuse as main transcriptc.1126-18255A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2BENST00000609686.4 linkuse as main transcriptc.1126-18255A>G intron_variant 1 NM_000834.5 P1
GRIN2BENST00000630791.2 linkuse as main transcriptc.1126-18255A>G intron_variant 5
GRIN2BENST00000636855.1 linkuse as main transcriptn.24-660A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0351
AC:
5348
AN:
152218
Hom.:
218
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00567
Gnomad AMI
AF:
0.0175
Gnomad AMR
AF:
0.0230
Gnomad ASJ
AF:
0.0498
Gnomad EAS
AF:
0.200
Gnomad SAS
AF:
0.112
Gnomad FIN
AF:
0.103
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0267
Gnomad OTH
AF:
0.0325
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0350
AC:
5337
AN:
152336
Hom.:
217
Cov.:
32
AF XY:
0.0405
AC XY:
3019
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00565
Gnomad4 AMR
AF:
0.0229
Gnomad4 ASJ
AF:
0.0498
Gnomad4 EAS
AF:
0.200
Gnomad4 SAS
AF:
0.110
Gnomad4 FIN
AF:
0.103
Gnomad4 NFE
AF:
0.0267
Gnomad4 OTH
AF:
0.0331
Alfa
AF:
0.0339
Hom.:
365
Bravo
AF:
0.0273
Asia WGS
AF:
0.135
AC:
467
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.12
DANN
Benign
0.38

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: rs2160519; hg19: chr12-13787846; API