rs201228929
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000834.5(GRIN2B):āc.1023T>Cā(p.Asn341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,564,038 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 (ā ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.0000071 ( 0 hom. )
Consequence
GRIN2B
NM_000834.5 synonymous
NM_000834.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.40
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 12-13675847-A-G is Benign according to our data. Variant chr12-13675847-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.4 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000591 (9/152166) while in subpopulation AFR AF= 0.000193 (8/41442). AF 95% confidence interval is 0.0000957. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.1023T>C | p.Asn341= | synonymous_variant | 5/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.1023T>C | p.Asn341= | synonymous_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.1023T>C | p.Asn341= | synonymous_variant | 5/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000630791.2 | c.1023T>C | p.Asn341= | synonymous_variant | 6/8 | 5 | |||
GRIN2B | ENST00000636856.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249928Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135088
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GnomAD4 exome AF: 0.00000708 AC: 10AN: 1411872Hom.: 0 Cov.: 25 AF XY: 0.00000567 AC XY: 4AN XY: 705422
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2020 | - - |
Computational scores
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Name
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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