rs2192972

chr12-13679582-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.1011-3723A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,174 control chromosomes in the GnomAD database, including 2,207 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 0.16 (2207 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2B	NM_000834.5	c.1011-3723A>C		intron_variant		ENST00000609686.4
GRIN2B	NM_001413992.1	c.1011-3723A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2B	ENST00000609686.4	c.1011-3723A>C		intron_variant		1	NM_000834.5	P1
GRIN2B	ENST00000630791.2	c.1011-3723A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25075 AN: 152054 Hom.: 2208 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.165 AC: 25083 AN: 152174 Hom.: 2207 Cov.: 32 AF XY: 0.168 AC XY: 12493 AN XY: 74382

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.142

Alfa AF: 0.172 Hom.: 2157

Bravo AF: 0.156

Asia WGS AF: 0.175 AC: 607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	10
Dann	Benign	0.71

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: rs2192972; hg19: chr12-13832516;