12-13617256-G-C

Position:

• chr12-13617256-G-C

Variant summary

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

The NM_000834.5(GRIN2B):​c.1126-599C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,128 control chromosomes in the GnomAD database, including 11,163 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 0.36 (11163 hom., cov: 33)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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]

(HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2B	NM_000834.5	c.1126-599C>G		intron_variant		ENST00000609686.4
LOC105369668	XR_001749013.2	n.613+2030G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2B	ENST00000609686.4	c.1126-599C>G		intron_variant		1	NM_000834.5	P1
	ENST00000652867.1	n.331+2030G>C		intron_variant, non_coding_transcript_variant
GRIN2B	ENST00000630791.2	c.1126-599C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54328 AN: 152010 Hom.: 11158 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.357 AC: 54352 AN: 152128 Hom.: 11163 Cov.: 33 AF XY: 0.370 AC XY: 27521 AN XY: 74354

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.357

Alfa AF: 0.247 Hom.: 670

Bravo AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1805539; hg19: chr12-13770190;