12-13552958-T-C

Position:

• chr12-13552958-T-C

Variant summary

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

The NM_000834.5(GRIN2B):​c.*9825A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,038 control chromosomes in the GnomAD database, including 28,111 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 0.56 (28111 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GRIN2B NM_000834.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.*9825A>G		3_prime_UTR_variant	14/14	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.*9825A>G		3_prime_UTR_variant	15/15		NP_001400921.1
GRIN2B	XM_005253351.3	c.*9825A>G		3_prime_UTR_variant	4/4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686	c.*9825A>G		3_prime_UTR_variant	14/14	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000637214.1	c.69+55645A>G		intron_variant		5		ENSP00000489997.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85660 AN: 151918 Hom.: 28095 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.564 AC: 85690 AN: 152036 Hom.: 28111 Cov.: 32 AF XY: 0.569 AC XY: 42261 AN XY: 74288

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.629

Alfa AF: 0.681 Hom.: 17970

Bravo AF: 0.552

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.2
DANN	Benign	0.83

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: rs2160517; hg19: chr12-13705892;