rs4763361

Variant names:

• chr12-13966926-C-G
• rs4763361
• NM_000834.5:c.-19+13002G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-13966926-C-G
• chr12-13966926-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.-19+13002G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 152,196 control chromosomes in the GnomAD database, including 64,830 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 0.92 (64830 hom., cov: 31)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.-19+13002G>C		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.-19+13002G>C		intron_variant	Intron 2 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.3	c.-19+13002G>C		intron_variant	Intron 3 of 14	5		ENSP00000486677.3
GRIN2B	ENST00000627535.2	c.-19+13002G>C		intron_variant	Intron 2 of 2	5		ENSP00000486411.1
GRIN2B	ENST00000714048.1	n.-19+13002G>C		intron_variant	Intron 2 of 12			ENSP00000519339.1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139444 AN: 152078 Hom.: 64798 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.917 AC: 139532 AN: 152196 Hom.: 64830 Cov.: 31 AF XY: 0.918 AC XY: 68313 AN XY: 74412

African (AFR) AF: 0.750 AC: 31084 AN: 41470

American (AMR) AF: 0.963 AC: 14729 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 0.861 AC: 4451 AN: 5168

South Asian (SAS) AF: 0.962 AC: 4636 AN: 4818

European-Finnish (FIN) AF: 0.995 AC: 10561 AN: 10612

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67462 AN: 68038

Other (OTH) AF: 0.923 AC: 1950 AN: 2112

Alfa AF: 0.949 Hom.: 8667

Bravo AF: 0.907

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.23
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: rs4763361; hg19: chr12-14119860;