rs11055612

Variant names:

• chr12-13770394-C-T
• rs11055612
• NM_000834.5:c.412-16479G>A

Variant summary

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

The NM_000834.5(GRIN2B):​c.412-16479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,992 control chromosomes in the GnomAD database, including 18,338 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 0.49 (18338 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.412-16479G>A		intron_variant	Intron 3 of 13	ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.412-16479G>A		intron_variant	Intron 3 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.3	c.412-16479G>A		intron_variant	Intron 4 of 14	5		ENSP00000486677.3
GRIN2B	ENST00000714048.1	n.412-16479G>A		intron_variant	Intron 3 of 12			ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73660 AN: 151874 Hom.: 18297 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.485 AC: 73765 AN: 151992 Hom.: 18338 Cov.: 32 AF XY: 0.474 AC XY: 35225 AN XY: 74286

African (AFR) AF: 0.575 AC: 23841 AN: 41464

American (AMR) AF: 0.415 AC: 6348 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5172

South Asian (SAS) AF: 0.359 AC: 1727 AN: 4812

European-Finnish (FIN) AF: 0.387 AC: 4072 AN: 10524

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33271 AN: 67952

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.485 Hom.: 40078

Bravo AF: 0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11055612; hg19: chr12-13923328;