chr12-13766280-T-G

Position:

• chr12-13766280-T-G

Variant summary

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

The NM_000834.5(GRIN2B):​c.412-12365A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,084 control chromosomes in the GnomAD database, including 17,427 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 0.47 (17427 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.412-12365A>C		intron_variant		ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.412-12365A>C		intron_variant		1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000630791.2	c.412-12365A>C		intron_variant		5		ENSP00000486677

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71354 AN: 151966 Hom.: 17400 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.470 AC: 71438 AN: 152084 Hom.: 17427 Cov.: 32 AF XY: 0.459 AC XY: 34105 AN XY: 74340

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.485

Alfa AF: 0.504 Hom.: 2464

Bravo AF: 0.465

Asia WGS AF: 0.345 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.61

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: rs2284416; hg19: chr12-13919214;