12-13982130-T-G

Position:

• chr12-13982130-T-G

Variant summary

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

The NM_001413992.1(GRIN2B):​c.-897A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 149,630 control chromosomes in the GnomAD database, including 59,314 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 0.89 (59314 hom., cov: 23)
• Consequence: GRIN2B NM_001413992.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_001413992.1	c.-897A>C		5_prime_UTR_variant	1/15		NP_001400921.1
GRIN2B	NM_001413993.1	c.-468A>C		5_prime_UTR_variant	1/4		NP_001400922.1
		n.13982130T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.886 AC: 132459 AN: 149524 Hom.: 59280 Cov.: 23

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.895

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.886 AC: 132543 AN: 149630 Hom.: 59314 Cov.: 23 AF XY: 0.879 AC XY: 64153 AN XY: 72990

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.892

Alfa AF: 0.919 Hom.: 4956

Bravo AF: 0.879

Asia WGS AF: 0.737 AC: 2553 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764028; hg19: chr12-14135064;