rs142203984
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000834.5(GRIN2B):c.771C>T(p.Ile257Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,614,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 1 hom. )
Consequence
GRIN2B
NM_000834.5 synonymous
NM_000834.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.302
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 12-13753556-G-A is Benign according to our data. Variant chr12-13753556-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 71487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.302 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000145 (212/1461822) while in subpopulation EAS AF= 0.00139 (55/39700). AF 95% confidence interval is 0.00109. There are 1 homozygotes in gnomad4_exome. There are 124 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GRIN2B | NM_000834.5 | c.771C>T | p.Ile257Ile | synonymous_variant | Exon 4 of 14 | ENST00000609686.4 | NP_000825.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GRIN2B | ENST00000609686.4 | c.771C>T | p.Ile257Ile | synonymous_variant | Exon 4 of 14 | 1 | NM_000834.5 | ENSP00000477455.1 | ||
| GRIN2B | ENST00000630791.2 | c.771C>T | p.Ile257Ile | synonymous_variant | Exon 5 of 8 | 5 | ENSP00000486677.3 |
Frequencies
GnomAD3 genomes 0.0000986 AC: 15AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000295 AC: 74AN: 251026Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135650
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GnomAD4 exome AF: 0.000145 AC: 212AN: 1461822Hom.: 1 Cov.: 32 AF XY: 0.000171 AC XY: 124AN XY: 727216
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GnomAD4 genome 0.0000985 AC: 15AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Aug 07, 2017
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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
Dec 19, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at