chr12-13562374-A-C
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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
NM_000834.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0780
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 |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.*409T>G | 3_prime_UTR_variant | 14/14 | ENST00000609686.4 | ||
GRIN2B | NM_001413992.1 | c.*409T>G | 3_prime_UTR_variant | 15/15 | |||
GRIN2B | XM_005253351.3 | c.*409T>G | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.*409T>G | 3_prime_UTR_variant | 14/14 | 1 | NM_000834.5 | P1 | ||
GRIN2B | ENST00000637214.1 | c.69+46229T>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.378 AC: 57427AN: 151944Hom.: 13156 Cov.: 32
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GnomAD4 exome AF: 0.424 AC: 20070AN: 47320Hom.: 4765 Cov.: 0 AF XY: 0.421 AC XY: 10003AN XY: 23770
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GnomAD4 genome AF: 0.378 AC: 57432AN: 152062Hom.: 13159 Cov.: 32 AF XY: 0.375 AC XY: 27860AN XY: 74312
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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 submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2021 | This variant is associated with the following publications: (PMID: 26257337) - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at