rs220557

Positions:

• chr12-13794846-A-C
• chr12-13794846-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000834.5(GRIN2B):​c.412-40931T>G variant causes a intron change. The variant allele was found at a frequency of 0.409 in 152,056 control chromosomes in the GnomAD database, including 13,247 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 0.41 (13247 hom., cov: 33)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.412-40931T>G		intron_variant		ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.412-40931T>G		intron_variant		1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000630791.2	c.412-40931T>G		intron_variant		5		ENSP00000486677

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62145 AN: 151938 Hom.: 13225 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.409 AC: 62211 AN: 152056 Hom.: 13247 Cov.: 33 AF XY: 0.407 AC XY: 30292 AN XY: 74338

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.378

Alfa AF: 0.357 Hom.: 9715

Bravo AF: 0.425

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.78

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: rs220557; hg19: chr12-13947780;