rs219931

Positions:

• chr12-13956753-G-A

Variant summary

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

The NM_000834.5(GRIN2B):​c.-19+23175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,040 control chromosomes in the GnomAD database, including 44,920 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 0.76 (44920 hom., cov: 31)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.-19+23175C>T		intron_variant		ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.-19+23175C>T		intron_variant		1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000627535.2	c.-19+23175C>T		intron_variant		5		ENSP00000486411
GRIN2B	ENST00000630791.2	c.-19+23175C>T		intron_variant		5		ENSP00000486677

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115838 AN: 151922 Hom.: 44898 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.762 AC: 115921 AN: 152040 Hom.: 44920 Cov.: 31 AF XY: 0.756 AC XY: 56182 AN XY: 74316

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.755

Alfa AF: 0.831 Hom.: 28316

Bravo AF: 0.743

Asia WGS AF: 0.670 AC: 2330 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.82

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: rs219931; hg19: chr12-14109687;