rs4764043

chr12-13962548-C-T

Variant summary

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

The NM_000834.5(GRIN2B):c.-19+17380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 152,310 control chromosomes in the GnomAD database, including 264 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 0.050 (264 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2B	NM_000834.5	c.-19+17380G>A		intron_variant		ENST00000609686.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2B	ENST00000609686.4	c.-19+17380G>A		intron_variant		1	NM_000834.5	P1
GRIN2B	ENST00000627535.2	c.-19+17380G>A		intron_variant		5
GRIN2B	ENST00000630791.2	c.-19+17380G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7541 AN: 152192 Hom.: 267 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0495 AC: 7543 AN: 152310 Hom.: 264 Cov.: 32 AF XY: 0.0492 AC XY: 3663 AN XY: 74482

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0430

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0656 Hom.: 786

Bravo AF: 0.0452

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	12
Dann	Benign	0.67

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: rs4764043; hg19: chr12-14115482;