rs2192970

Variant names:

• chr12-13683379-G-A
• rs2192970
• NM_000834.5:c.1011-7520C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-13683379-G-A
• chr12-13683379-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000834.5(GRIN2B):​c.1011-7520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,112 control chromosomes in the GnomAD database, including 2,100 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 0.15 (2100 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 11 publications found

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]

RN7SKP162 (HGNC:45886): (RN7SK pseudogene 162)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000834.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	NM_000834.5	MANE Select	c.1011-7520C>T		intron	N/A	NP_000825.2
	GRIN2B	NM_001413992.1		c.1011-7520C>T		intron	N/A	NP_001400921.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	ENST00000609686.4	TSL:1 MANE Select	c.1011-7520C>T		intron	N/A	ENSP00000477455.1
	GRIN2B	ENST00000630791.3	TSL:5	c.1011-7520C>T		intron	N/A	ENSP00000486677.3
	GRIN2B	ENST00000714048.1		n.1011-7520C>T		intron	N/A	ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23251 AN: 151994 Hom.: 2100 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.153 AC: 23247 AN: 152112 Hom.: 2100 Cov.: 32 AF XY: 0.150 AC XY: 11132 AN XY: 74328

African (AFR) AF: 0.0783 AC: 3253 AN: 41526

American (AMR) AF: 0.175 AC: 2675 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5172

South Asian (SAS) AF: 0.125 AC: 601 AN: 4812

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13727 AN: 67982

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.0830 Hom.: 133

Bravo AF: 0.154

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.51
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2192970; hg19: chr12-13836313;