rs10845852

Variant names:

• chr12-13874203-C-A
• rs10845852
• NM_000834.5:c.-18-7977G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-13874203-C-A
• chr12-13874203-C-G
• chr12-13874203-C-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.-18-7977G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,130 control chromosomes in the GnomAD database, including 3,017 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 0.19 (3017 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 7 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]

GRIN2B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• developmental and epileptic encephalopathy, 27

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability, autosomal dominant 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.-18-7977G>T		intron_variant	Intron 2 of 13	ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.-18-7977G>T		intron_variant	Intron 2 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.3	c.-18-7977G>T		intron_variant	Intron 3 of 14	5		ENSP00000486677.3
GRIN2B	ENST00000627535.2	c.-18-7977G>T		intron_variant	Intron 2 of 2	5		ENSP00000486411.1
GRIN2B	ENST00000714048.1	n.-18-7977G>T		intron_variant	Intron 2 of 12			ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28973 AN: 152012 Hom.: 3012 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.191 AC: 28999 AN: 152130 Hom.: 3017 Cov.: 32 AF XY: 0.194 AC XY: 14408 AN XY: 74366

African (AFR) AF: 0.273 AC: 11332 AN: 41468

American (AMR) AF: 0.130 AC: 1993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3468

East Asian (EAS) AF: 0.163 AC: 840 AN: 5162

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4826

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10326 AN: 68016

Other (OTH) AF: 0.174 AC: 367 AN: 2114

Alfa AF: 0.153 Hom.: 3250

Bravo AF: 0.185

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.098
DANN	Benign	0.52
PhyloP100		-0.39
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: rs10845852; hg19: chr12-14027137;