12-13744527-G-T

Position:

• chr12-13744527-G-T

Variant summary

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

The NM_000834.5(GRIN2B):​c.1010+8790C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,102 control chromosomes in the GnomAD database, including 1,965 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 0.13 (1965 hom., cov: 32)
• Consequence: GRIN2B NM_000834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.1010+8790C>A		intron_variant		ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.1010+8790C>A		intron_variant			NP_001400921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.1010+8790C>A		intron_variant		1	NM_000834.5	ENSP00000477455.1
GRIN2B	ENST00000630791.2	c.1010+8790C>A		intron_variant		5		ENSP00000486677.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19925 AN: 151984 Hom.: 1961 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.131 AC: 19936 AN: 152102 Hom.: 1965 Cov.: 32 AF XY: 0.136 AC XY: 10078 AN XY: 74358

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.0919

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.144

Alfa AF: 0.145 Hom.: 2558

Bravo AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.70

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: rs2268122; hg19: chr12-13897461;