rs731086

Positions:

• chr12-13580795-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000834.5(GRIN2B):​c.2011-8831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,184 control chromosomes in the GnomAD database, including 7,380 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 0.27 (7380 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.2011-8831T>C		intron_variant		ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.2011-8831T>C		intron_variant			NP_001400921.1
GRIN2B	XM_005253351.3	c.-43-10778T>C		intron_variant			XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.2011-8831T>C		intron_variant		1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000637214.1	c.69+27808T>C		intron_variant		5		ENSP00000489997.1
GRIN2B	ENST00000628166.2	n.271-8831T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41734 AN: 152066 Hom.: 7372 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.274 AC: 41741 AN: 152184 Hom.: 7380 Cov.: 32 AF XY: 0.269 AC XY: 20008 AN XY: 74404

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.330

Alfa AF: 0.321 Hom.: 1355

Bravo AF: 0.280

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs731086; hg19: chr12-13733729;