NM_000834.5:c.*15141C>A

Variant names:

• chr12-13547642-G-T
• rs12814951
• NM_000834.5:c.*15141C>A

Variant summary

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

The NM_000834.5(GRIN2B):​c.*15141C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,944 control chromosomes in the GnomAD database, including 11,584 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 0.35 (11584 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: GRIN2B NM_000834.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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]

ENSG00000256306 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.*15141C>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.*15141C>A		3_prime_UTR_variant	Exon 15 of 15		NP_001400921.1
GRIN2B	XM_005253351.3	c.*15141C>A		3_prime_UTR_variant	Exon 4 of 4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686	c.*15141C>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000637214.1	c.69+60961C>A		intron_variant	Intron 1 of 1	5		ENSP00000489997.1
ENSG00000256306	ENST00000543347.1	n.*60G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53911 AN: 151828 Hom.: 11580 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.410

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.355 AC: 53919 AN: 151944 Hom.: 11584 Cov.: 31 AF XY: 0.354 AC XY: 26312 AN XY: 74232

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.409

Alfa AF: 0.457 Hom.: 21574

Bravo AF: 0.352

Asia WGS AF: 0.242 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.74

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: rs12814951; hg19: chr12-13700576;