rs4522263

chr12-13559541-C-Gchr12-13559541-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000834.5(GRIN2B):c.*3242G>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 0.0589 in 152,248 control chromosomes in the GnomAD database, including 373 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 0.059 (373 hom., cov: 33)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: GRIN2B NM_000834.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2B	NM_000834.5	c.*3242G>C		3_prime_UTR_variant	14/14	ENST00000609686.4
GRIN2B	NM_001413992.1	c.*3242G>C		3_prime_UTR_variant	15/15
GRIN2B	XM_005253351.3	c.*3242G>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2B	ENST00000609686.4	c.*3242G>C		3_prime_UTR_variant	14/14	1	NM_000834.5	P1
GRIN2B	ENST00000637214.1	c.69+49062G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8980 AN: 152112 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.111 AC: 2 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0589 AC: 8970 AN: 152230 Hom.: 373 Cov.: 33 AF XY: 0.0614 AC XY: 4568 AN XY: 74416

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0532 Hom.: 40

Bravo AF: 0.0565

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.44
Dann	Benign	0.63

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: rs4522263; hg19: chr12-13712475;