12-13702698-G-C

Variant names:

• chr12-13702698-G-C
• rs1012586
• NM_000834.5:c.1011-26839C>G

Variant summary

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

The NM_000834.5(GRIN2B):​c.1011-26839C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,894 control chromosomes in the GnomAD database, including 9,790 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 0.34 (9790 hom., cov: 31)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.1011-26839C>G		intron_variant	Intron 4 of 13	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.1011-26839C>G		intron_variant	Intron 5 of 14		NP_001400921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.1011-26839C>G		intron_variant	Intron 4 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.2	c.1011-26839C>G		intron_variant	Intron 5 of 7	5		ENSP00000486677.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52339 AN: 151776 Hom.: 9767 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.345 AC: 52395 AN: 151894 Hom.: 9790 Cov.: 31 AF XY: 0.357 AC XY: 26502 AN XY: 74238

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.353

Alfa AF: 0.187 Hom.: 421

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.64

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: rs1012586; hg19: chr12-13855632;