12-13980398-C-T

Variant names:

• chr12-13980398-C-T
• rs3764030
• NM_000834.5:c.-447-42G>A

Variant summary

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

The NM_001413995.1(GRIN2B):​c.-489G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,984 control chromosomes in the GnomAD database, including 3,318 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 0.18 (3318 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: GRIN2B NM_001413995.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.-447-42G>A		intron_variant	Intron 1 of 13	ENST00000609686.4	NP_000825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.-447-42G>A		intron_variant	Intron 1 of 13	1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.2	c.-447-42G>A		intron_variant	Intron 2 of 7	5		ENSP00000486677.3
GRIN2B	ENST00000627535.2	c.-447-42G>A		intron_variant	Intron 1 of 2	5		ENSP00000486411.1
GRIN2B	ENST00000681855.1	n.130-42G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27098 AN: 151852 Hom.: 3318 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.143 AC: 2 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.178 AC: 27099 AN: 151970 Hom.: 3318 Cov.: 32 AF XY: 0.182 AC XY: 13492 AN XY: 74274

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.216

Alfa AF: 0.208 Hom.: 4924

Bravo AF: 0.194

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3764030; hg19: chr12-14133332;