ENST00000637214.1:c.70-50761G>T

Variant names:

• chr12-13488772-C-A
• rs1457614
• ENST00000637214.1:c.70-50761G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637214.1(GRIN2B):​c.70-50761G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,144 control chromosomes in the GnomAD database, including 42,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42091 hom., cov: 33)
• Consequence: GRIN2B ENST00000637214.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 6 publications found

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]

GRIN2B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• developmental and epileptic encephalopathy, 27

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability, autosomal dominant 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000637214.1	c.70-50761G>T		intron_variant	Intron 1 of 1	5		ENSP00000489997.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112018 AN: 152026 Hom.: 42051 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.772

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 112110 AN: 152144 Hom.: 42091 Cov.: 33 AF XY: 0.739 AC XY: 54962 AN XY: 74384

African (AFR) AF: 0.585 AC: 24235 AN: 41456

American (AMR) AF: 0.799 AC: 12217 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2696 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4069 AN: 5180

South Asian (SAS) AF: 0.787 AC: 3795 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8069 AN: 10588

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54640 AN: 68012

Other (OTH) AF: 0.775 AC: 1637 AN: 2112

Alfa AF: 0.785 Hom.: 83407

Bravo AF: 0.731

Asia WGS AF: 0.790 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.20
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1457614; hg19: chr12-13641706;