NM_000834.5:c.*1536T>C

Variant names:

• chr12-13561247-A-G
• rs1805502
• NM_000834.5:c.*1536T>C

Variant summary

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

The NM_000834.5(GRIN2B):​c.*1536T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,492 control chromosomes in the GnomAD database, including 5,724 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 0.25 (5724 hom., cov: 30)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: GRIN2B NM_000834.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 46 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	NM_000834.5	MANE Select	c.*1536T>C		3_prime_UTR	Exon 14 of 14	NP_000825.2	Q13224
	GRIN2B	NM_001413992.1		c.*1536T>C		3_prime_UTR	Exon 15 of 15	NP_001400921.1	A0A8D9PHB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	ENST00000609686.4	TSL:1 MANE Select	c.*1536T>C		3_prime_UTR	Exon 14 of 14	ENSP00000477455.1	Q13224
	GRIN2B	ENST00000630791.3	TSL:5	c.*1536T>C		3_prime_UTR	Exon 15 of 15	ENSP00000486677.3	A0A0D9SFK0
	GRIN2B	ENST00000637214.1	TSL:5	c.69+47356T>C		intron	N/A	ENSP00000489997.1	A0A1B0GU78

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37898 AN: 151362 Hom.: 5698 Cov.: 30

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.251 AC: 37965 AN: 151480 Hom.: 5724 Cov.: 30 AF XY: 0.247 AC XY: 18259 AN XY: 74072

African (AFR) AF: 0.427 AC: 17497 AN: 40970

American (AMR) AF: 0.180 AC: 2742 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.182 AC: 938 AN: 5144

South Asian (SAS) AF: 0.236 AC: 1133 AN: 4808

European-Finnish (FIN) AF: 0.188 AC: 1987 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12471 AN: 67944

Other (OTH) AF: 0.212 AC: 446 AN: 2102

Alfa AF: 0.201 Hom.: 14958

Bravo AF: 0.255

Asia WGS AF: 0.217 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		0.16
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: rs1805502; hg19: chr12-13714181;