rs146792012
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000609686.4(GRIN2B):c.4113C>T(p.Tyr1371=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000241 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
GRIN2B
ENST00000609686.4 synonymous
ENST00000609686.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.79
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=-0.47).
BP6
Variant 12-13563125-G-A is Benign according to our data. Variant chr12-13563125-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 245622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000302 (46/152334) while in subpopulation AMR AF= 0.00118 (18/15306). AF 95% confidence interval is 0.00076. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.4113C>T | p.Tyr1371= | synonymous_variant | 14/14 | ENST00000609686.4 | NP_000825.2 | |
GRIN2B | NM_001413992.1 | c.4113C>T | p.Tyr1371= | synonymous_variant | 15/15 | NP_001400921.1 | ||
GRIN2B | XM_005253351.3 | c.1899C>T | p.Tyr633= | synonymous_variant | 4/4 | XP_005253408.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.4113C>T | p.Tyr1371= | synonymous_variant | 14/14 | 1 | NM_000834.5 | ENSP00000477455 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+45478C>T | intron_variant | 5 | ENSP00000489997 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152216Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251458Hom.: 0 AF XY: 0.000235 AC XY: 32AN XY: 135912
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GnomAD4 exome AF: 0.000235 AC: 343AN: 1461852Hom.: 0 Cov.: 33 AF XY: 0.000227 AC XY: 165AN XY: 727240
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GnomAD4 genome AF: 0.000302 AC: 46AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 29, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | GRIN2B: BP4 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at