chr12-13562374-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000834.5(GRIN2B):​c.*409T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 199,382 control chromosomes in the GnomAD database, including 17,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13159 hom., cov: 32)
Exomes 𝑓: 0.42 ( 4765 hom. )

Consequence

GRIN2B
NM_000834.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0780
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 12-13562374-A-C is Benign according to our data. Variant chr12-13562374-A-C is described in ClinVar as [Benign]. Clinvar id is 1281683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2BNM_000834.5 linkuse as main transcriptc.*409T>G 3_prime_UTR_variant 14/14 ENST00000609686.4
GRIN2BNM_001413992.1 linkuse as main transcriptc.*409T>G 3_prime_UTR_variant 15/15
GRIN2BXM_005253351.3 linkuse as main transcriptc.*409T>G 3_prime_UTR_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2BENST00000609686.4 linkuse as main transcriptc.*409T>G 3_prime_UTR_variant 14/141 NM_000834.5 P1
GRIN2BENST00000637214.1 linkuse as main transcriptc.69+46229T>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.378
AC:
57427
AN:
151944
Hom.:
13156
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.116
Gnomad AMI
AF:
0.411
Gnomad AMR
AF:
0.484
Gnomad ASJ
AF:
0.516
Gnomad EAS
AF:
0.216
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.434
Gnomad MID
AF:
0.630
Gnomad NFE
AF:
0.513
Gnomad OTH
AF:
0.437
GnomAD4 exome
AF:
0.424
AC:
20070
AN:
47320
Hom.:
4765
Cov.:
0
AF XY:
0.421
AC XY:
10003
AN XY:
23770
show subpopulations
Gnomad4 AFR exome
AF:
0.0884
Gnomad4 AMR exome
AF:
0.497
Gnomad4 ASJ exome
AF:
0.477
Gnomad4 EAS exome
AF:
0.209
Gnomad4 SAS exome
AF:
0.282
Gnomad4 FIN exome
AF:
0.407
Gnomad4 NFE exome
AF:
0.473
Gnomad4 OTH exome
AF:
0.441
GnomAD4 genome
AF:
0.378
AC:
57432
AN:
152062
Hom.:
13159
Cov.:
32
AF XY:
0.375
AC XY:
27860
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.485
Gnomad4 ASJ
AF:
0.516
Gnomad4 EAS
AF:
0.216
Gnomad4 SAS
AF:
0.293
Gnomad4 FIN
AF:
0.434
Gnomad4 NFE
AF:
0.513
Gnomad4 OTH
AF:
0.436
Alfa
AF:
0.492
Hom.:
32149
Bravo
AF:
0.374
Asia WGS
AF:
0.250
AC:
872
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 24, 2021This variant is associated with the following publications: (PMID: 26257337) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.7
DANN
Benign
0.72

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.

Other links and lift over

dbSNP: rs890; hg19: chr12-13715308; API